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1. Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia

Author: Damien Grapton, Marie-Alexandra Alyanakian, Virginie Pascal, Michael Dussiot, Tomas Leanderson, Thiago Trovati Maciel, Olivier Hermine, Marc Benhamou, Séverine Coulon, Renato C. Monteiro, Patrick Mayeux, Kamel Djedaini, Zeliha Oruc, Julie Vandekerckhove, Saurabh Agarwal, Meetu Kaushik Tiwari, Michel Cogné, Ivan C. Moura, Bertrand Arnulf, Houda Tamouza, Geneviève Courtois, Aurélie Fricot, Pamella Huey Mei Wang, Yael Zermati, Jean-Antoine Ribeil, Céline Callens, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Différenciation des cellules B, hémopathies, lymphoïdes et déficit de l'immunité humorale, Université Paris Diderot - Paris 7 (UPD7), Tolérance immunitaire et présentation antigénique: impact en auto-immunité et en transplantation, Institut Cochin (UMR_S567 / UMR 8104), Université de Limoges (UNILIM), Service d Hématologie, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 ( UPD7 ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université de Limoges ( UNILIM ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and Slama, Catherine
Subjects: Ineffective erythropoiesis, MESH: Signal Transduction, MESH: Anemia, Erythroblasts, MESH: Mice, Inbred NOD, MESH: Anoxia, Mice, SCID, medicine.disease_cause, Mice, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Mice, Inbred NOD, hemic and lymphatic diseases, MESH : Cell Proliferation, MESH : Erythropoietin, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Erythropoiesis, MESH: Animals, MESH: Mice, SCID, MESH: Erythroblasts, Hypoxia, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 0303 health sciences, Transferrin, Anemia, General Medicine, MESH : Transferrin, MESH : Mice, Transgenic, 3. Good health, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Mitogen-Activated Protein Kinases, MESH: Transferrin, medicine.drug, Signal Transduction, MESH: Cells, Cultured, MESH : Anoxia, MESH: Mice, Transgenic, MESH : Anemia, Transferrin receptor, Mice, Transgenic, MESH : Immunoglobulin A, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, MESH : Erythropoiesis, Erythroblast, MESH: Cell Proliferation, Receptors, Transferrin, MESH : Mice, MESH : Cells, Cultured, medicine, Animals, Humans, MESH : Receptors, Transferrin, MESH: Receptors, Transferrin, MESH: Erythropoietin, MESH: Immunoglobulin A, Erythropoietin, MESH: Mice, PI3K/AKT/mTOR pathway, 030304 developmental biology, Cell Proliferation, MESH : Signal Transduction, MESH: Humans, MESH : Mice, Inbred NOD, MESH : Humans, MESH: Erythropoiesis, MESH : Mitogen-Activated Protein Kinases, MESH : Phosphatidylinositol 3-Kinases, MESH : Erythroblasts, medicine.disease, MESH: Mitogen-Activated Protein Kinases, MESH : Mice, SCID, Immunoglobulin A, chemistry, MESH: Phosphatidylinositol 3-Kinases, Immunology, Cancer research, MESH : Animals
Abstract: International audience; Anemia because of insufficient production of and/or response to erythropoietin (Epo) is a major complication of chronic kidney disease and cancer. The mechanisms modulating the sensitivity of erythroblasts to Epo remain poorly understood. We show that, when cultured with Epo at suboptimal concentrations, the growth and clonogenic potential of erythroblasts was rescued by transferrin receptor 1 (TfR1)-bound polymeric IgA1 (pIgA1). Under homeostatic conditions, erythroblast numbers were increased in mice expressing human IgA1 compared to control mice. Hypoxic stress of these mice led to increased amounts of pIgA1 and erythroblast expansion. Expression of human IgA1 or treatment of wild-type mice with the TfR1 ligands pIgA1 or iron-loaded transferrin (Fe-Tf) accelerated recovery from acute anemia. TfR1 engagement by either pIgA1 or Fe-Tf increased cell sensitivity to Epo by inducing activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. These cellular responses were mediated through the TfR1-internalization motif, YXXΦ. Our results show that pIgA1 and TfR1 are positive regulators of erythropoiesis in both physiological and pathological situations. Targeting this pathway may provide alternate approaches to the treatment of ineffective erythropoiesis and anemia.
Published: 2011
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2. Efficacy of L-asparaginase with methotexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase II study

Author: Jaccard, Arnaud, Gachard, Nathalie, Marin, Benoît, Rogez, Sylvie, Audrain, Marie, Suarez, Felipe, Tilly, Hervé, Morschhauser, Franck, Thieblemont, Catherine, Ysebaert, Loic, Devidas, Alain, Petit, Barbara, de Leval, Laurence, Gaulard, Philippe, Feuillard, Jean, Bordessoule, Dominique, Hermine, Olivier, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Groupe d'Étude sur les Géomatériaux et Environnements Naturels, Anthropiques et Archéologiques - EA 3795 ( GEGENAA ), SFR Condorcet, Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Reims Champagne-Ardenne ( URCA ) -Institut national de recherches archéologiques préventives ( Inrap ), Service hématologie Poitiers, Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Limoges ( UNILIM ), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Groupe d'Étude sur les Géomatériaux et Environnements Naturels, Anthropiques et Archéologiques - EA 3795 (GEGENAA), Université de Reims Champagne-Ardenne (URCA)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Limoges (UNILIM), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), Neuroépidémiologie Tropicale et Comparée (NETEC), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges (UNILIM), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], Laboratoire d'Immunologie, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), service d'Hématologie Oncologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] ( SIME ), Neuroépidémiologie Tropicale et Comparée ( NETEC ), Université de Limoges ( UNILIM ) -Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université de Limoges (UNILIM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Physiopathologie Toulouse Purpan (CPTP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio], [ SDV.IMM ] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Extranodal NK/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. No therapeutic strategy is currently identified in relapsing patients. We report the results of a French prospective phase II trial of an L-asparaginase-containing regimen in 19 patients with relapsed or refractory disease treated in 11 centers. Eleven patients were in relapse and 8 patients were refractory to their first line of treatment. L-asparaginase-based treatment yielded objective responses in 14 of the 18 evaluable patients after 3 cycles. Eleven patients entered complete remission (CR) (61%) and only four of them relapsed. The median overall survival time was 1 year, with a median response duration of 12 months. The main adverse events were hepatitis, cytopenia and allergy. Absence of anti-asparaginase antibodies and disappearance of EBV serum DNA were significantly associated with a better outcome. These data confirm the excellent activity of L-asparaginase-containing regimens in extranodal NK/T-cell lymphoma. L-asparaginase-based treatment should thus be considered for salvage therapy, especially in patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma warrants evaluation in prospective trials. This trial is registered at http://ClinicalTrials.gov as number NCT00283985.
Published: 2011
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3. Randomized Study of Intensified Anthracycline Doses for Induction and Recombinant Interleukin-2 for Maintenance in Patients With Acute Myeloid Leukemia Age 50 to 70 Years: Results of the ALFA-9801 Study

Author: Claude Preudhomme, Thierry de Revel, Dominique Bordessoule, Christine Terré, Sylvie Chevret, Mauricette Michallet, Pascal Turlure, Sylvie Castaigne, Xavier Thomas, Cécile Pautas, Hervé Dombret, Nathalie Contentin, Oumedaly Reman, Claude Gardin, Selim Corm, Jean-Henri Bourhis, Pierre Fenaux, Emmanuel Raffoux, Philippe Rousselot, Fatiha Merabet, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Pathologie et virologie moléculaire (PVM (UMR_7151)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service d'Hématologie biologique [CHU Limoges], Université de Limoges (UNILIM), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Pathologie et virologie moléculaire ( PVM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Université de Limoges ( UNILIM ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, CHU Versailles, Centre Hospitalier de Versailles (CHV), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Pathologie et virologie moléculaire (PVM), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne
Subjects: Male, Cancer Research, medicine.medical_specialty, Time Factors, Anthracycline, Daunorubicin, Kaplan-Meier Estimate, Gastroenterology, Risk Assessment, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Idarubicin, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, Aged, Proportional Hazards Models, Acute leukemia, business.industry, Induction chemotherapy, Myeloid leukemia, Middle Aged, Recombinant Proteins, 3. Good health, Surgery, Leukemia, Myeloid, Acute, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Cytarabine, Interleukin-2, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, 030215 immunology, medicine.drug
Abstract: Purpose In patients with acute myeloid leukemia (AML), induction chemotherapy is based on standard doses of anthracyclines and cytarabine. High doses of cytarabine have been reported as being too toxic for patients older than age 50 years, but few studies have evaluated intensified doses of anthracyclines. Patients and Methods In this randomized Acute Leukemia French Association 9801 (ALFA-9801) study, high doses of daunorubicin (DNR; 80 mg/m2/d × 3 days) or idarubicin (IDA4; 12 mg/m2/d × 4 days) were compared with standard doses of idarubicin (IDA3; 12 mg/m2/d × 3 days) for remission induction in patients age 50 to 70 years, with an event-free survival (EFS) end point. After two consolidation courses based on intermediate doses of cytarabine, patients in continuous remission were randomly assigned to receive or not receive maintenance therapy with recombinant interleukin-2 (rIL-2; 5 × 106 U/m2 × 5 days each month) for a total duration of 12 months. A total of 468 patients entered the study (median age, 60 years). Results Overall complete remission rate was 77% with significant differences among the three randomization arms (83%, 78%, and 70% in the IDA3, IDA4, and DNR arms, respectively; P = .04). However, no significant differences were observed in relapse incidence, EFS, or overall survival among the three arms. In the 161 patients randomly assigned for maintenance therapy, no difference in outcome was observed between the rIL-2 and the no further treatment arms. Conclusion Neither intensification of anthracycline doses nor maintenance with rIL-2 showed a significant impact on AML course, at least as scheduled in this trial.
Published: 2010
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4. Long-term follow-up of patients with newly diagnosed follicular lymphoma in the prerituximab era: effect of response quality on survival--A study from the groupe d'etude des lymphomes de l'adulte

Author: Emmanuelle Bachy, Pauline Brice, Richard Delarue, André Bosly, Charles Foussard, Corinne Haioun, Philippe Solal-Celigny, Steven Le Gouill, Christian Gisselbrecht, Nicole Brousse, Dominique Bordessoule, Hervé Tilly, Bernadette Corront, Gilles Salles, Bertrand Coiffier, Christian Allard, Alain Delmer, Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Hôtel-Dieu [Paris], Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'Hématologie biologique [CHU Limoges], Université de Limoges (UNILIM), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie, CRLCC Henri Becquerel, Université Catholique de Louvain (UCL), Département de pathologie, Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université Catholique de Louvain = Catholic University of Louvain (UCL), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Université de Limoges ( UNILIM ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Catholique de Louvain ( UCL ), Hospices Civils de Lyon ( HCL ), and Université Claude Bernard Lyon 1 ( UCBL )
Subjects: Cancer Research, Time Factors, Follicular lymphoma, Kaplan-Meier Estimate, Gastroenterology, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Belgium, Recurrence, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Prospective Studies, Young adult, Prospective cohort study, Lymphoma, Follicular, Remission Induction, Antibodies, Monoclonal, Middle Aged, 3. Good health, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, France, medicine.drug, Adult, medicine.medical_specialty, Combination therapy, Adolescent, Antineoplastic Agents, Risk Assessment, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Aged, Neoplasm Staging, Proportional Hazards Models, business.industry, Proportional hazards model, Patient Selection, Cancer, medicine.disease, Lymphoma, Surgery, business, 030215 immunology, Follow-Up Studies
Abstract: Purpose First-line treatment for patients with newly diagnosed follicular lymphoma (FL) still remains debated, even in the rituximab-based combination therapy era. Few studies have addressed the question whether complete remission (CR) translates into better survival. The aim of this study was to assess the long-term follow-up of prospectively treated patients with FL and the potential correlation between response quality to first-line treatment and overall survival (OS). Patients and Methods Data from 536 patients with FL with low (n = 193) or high (n = 343) tumor burden enrolled from October 1986 to May 1995 in the French and Belgian GELF86 studies were analyzed. Data from these trials have been previously reported for low–tumor burden and high–tumor burden patients. Results Median follow-up was 14.9 years, and median OS was 9.8 years. Treated patients who achieved a complete response (CR; n = 194; 45%) had a significant longer OS than those only reaching a partial response (PR; n = 168; 39%) throughout treatment (hazard ratio [HR], 0.55; 95% CI, 0.42 to 0.72; P < .001) in an univariate time-dependent Cox model. Similar findings were found when response to treatment (CR v PR) was adjusted for potentially confounding factors in a multivariate model (HR, 0.53; 95% CI, 0.38 to 0.73; P < .001). Conclusion These data provide a long follow-up of these patients' cohorts and indicate that a better response to first-line treatment translates into an improved survival for patients with FL. Therefore, response-adapted therapy aiming to achieve a CR should be considered as first-line treatment.
Published: 2009
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5. Very long-term outcome of acute promyelocytic leukemia after treatment wtih all trans retinoic acid and chemotherapy: the European APL Group experience

Author: Emmanuel Raffoux, Sylvie Castaigne, Miguel A. Sanz, Sylvie Chevret, Simona Lapusan, Dominique Bordessoule, Xavier Thomas, Stéphane de Botton, Agnès Guerci, Patrice Chevallier, Sandrine Meyer-Monard, Claude Gardin, Christian Recher, Consuelo Rayon, Norbert Ifrah, Nathalie Fegeux, Augustin Ferrant, Laurent Degos, Olivier Tournilhac, Norbert Vey, Jean-Yves Cahn, Eric Solary, Pierre Fenaux, Lionel Ades, Hervé Dombret, Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Fédération des maladies infectieuses, CHU Clermont-Ferrand, Hematology, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'Hématologie biologique [CHU Limoges], Université de Limoges (UNILIM), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Université de Limoges ( UNILIM ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Acute promyelocytic leukemia, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Immunology, Tretinoin, Biochemistry, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Leukemia, Promyelocytic, Acute, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Cumulative incidence, neoplasms, Aged, 030304 developmental biology, 0303 health sciences, Chemotherapy, Hematology, business.industry, Cytarabine, Cell Biology, Middle Aged, medicine.disease, Mercaptopurine, Chemotherapy regimen, 3. Good health, Surgery, Europe, Leukemia, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Follow-Up Studies, medicine.drug
Abstract: Acute promyelocytic leukemia (APL) is highly curable with the combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy (CT), but very long-term results of this treatment, when CT should be added to ATRA and the role of maintenance treatment, remain uncertain. In our APL93 trial that included 576 newly diagnosed APL patients, with a median follow-up of 10 years, 10-year survival was 77%. Maintenance treatment significantly reduced 10-year cumulative incidence of relapses, from 43.2% to 33%, 23.4%, and 13.4% with no maintenance, maintenance using intermittent ATRA, continuous 6 mercaptopurine plus methotrexate, and both treatments, respectively (P < .001). Maintenance particularly benefited patients with white blood cell (WBC) count higher than 5 × 109/L (5000/μL). Early addition of CT to ATRA significantly improved 10-year event-free survival (EFS), but without significant effect on overall survival (OS). The 10-year cumulative incidence of deaths in complete response (CR), resulting mainly from myelosuppression, was 5.7%, 15.4%, and 21.7% in patients younger than 55, 55 to 65, and older than 65 years, respectively, supporting the need for less myelosuppressive treatments, particularly for consolidation therapy. This study is registered at http://clinicaltrials.gov as NCT00599937.
Published: 2009
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6. Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg cells and normal B-lymphocytes

Author: Fabienne Meggetto, Alan Bénard, Nadine Cogne, Aurélie Chanut, Nathalie Faumont, Georges Delsol, Jean Feuillard, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Centre de Physiopathologie Toulouse Purpan, and Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH : Cell Line, MESH : Molecular Sequence Data, DNA Mutational Analysis, MESH: NF-kappa B, Apoptosis, MESH: Base Sequence, medicine.disease_cause, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH: Luciferases, Renilla, immune system diseases, hemic and lymphatic diseases, MESH : Hodgkin Disease, Tumor Cells, Cultured, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Viral Matrix Proteins, MESH: Genetic Variation, Reed-Sternberg Cells, MESH: DNA Mutational Analysis, MESH : Immunoblotting, MESH: Reed-Sternberg Cells, Oncogene Proteins, Genetics, B-Lymphocytes, 0303 health sciences, Mutation, MESH: Immunoblotting, MESH : Oncogene Proteins, NF-kappa B, Hematology, Transfection, Hodgkin Disease, MESH: Hodgkin Disease, MESH : NF-kappa B, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Mutation, MESH : Transfection, MESH: Mutation, MESH : Recombinant Fusion Proteins, Recombinant Fusion Proteins, Immunoblotting, Molecular Sequence Data, MESH : Luciferases, Renilla, MESH : DNA Mutational Analysis, Biology, MESH: Sequence Homology, Nucleic Acid, MESH : B-Lymphocytes, Cell Line, Viral Matrix Proteins, 03 medical and health sciences, MESH: Oncogene Proteins, stomatognathic system, MESH : Genetic Variation, Sequence Homology, Nucleic Acid, MESH: B-Lymphocytes, medicine, otorhinolaryngologic diseases, MESH: Recombinant Fusion Proteins, Animals, Humans, Hodgkin's Lymphoma, MESH : Sequence Homology, Nucleic Acid, MESH: Tumor Cells, Cultured, Luciferases, Renilla, 030304 developmental biology, MESH: Viral Matrix Proteins, MESH: Molecular Sequence Data, MESH: Humans, MESH : Reed-Sternberg Cells, Base Sequence, MESH: Apoptosis, MESH: Transfection, MESH : Humans, Genetic Variation, medicine.disease, Hodgkin's lymphoma, Epstein–Barr virus, Lymphoma, MESH: Cell Line, stomatognathic diseases, Reed–Sternberg cell, Cell culture, Cancer research, MESH : Base Sequence, MESH : Animals, Carcinogenesis, MESH : Apoptosis
Abstract: International audience; BACKGROUND: In Epstein-Barr virus-associated Hodgkin's lymphomas, neoplastic Reed-Sternberg cells and surrounding non-tumor B-cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-cells. DESIGN AND METHODS: Twelve LMP1 natural variants from Reed-Sternberg cells, non-tumor B-cells of Hodgkin's lymphomas and from B-cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 cells to search for relationships between LMP1 cellular origin and oncogenic properties as well as nuclear factor-kappaB activation, and apoptosis protection. RESULTS: LMP1 variants of Reed-Sternberg cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg cells, but inconstantly for LMP1-variants from non-tumor B-cells. Analysis of LMP1 variants from both normal B-cells and Reed-Sternberg cells indicates that protection against apoptosis through activation of nuclear factor-kappaB - whatever the cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. CONCLUSIONS: Taken together, our results demonstrate that preserved nuclear factor-kappaB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor cells in Hodgkin's lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg cells.
Published: 2009
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7. L-asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature

Author: Dominique Bordessoule, Benoît Marin, Claire Larroche, Alain Devidas, Arnaud Jaccard, Barbara Petit, Nathalie Gachard, Catherine Thieblemont, Felipe Suarez, P. Gaulard, V. Coiteux, Stephane Girault, Jean-Marc Zini, Olivier Hermine, Remy Gressin, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Université de Limoges (UNILIM), Laboratoire SUBATECH Nantes (SUBATECH), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Groupe d'Étude sur les Géomatériaux et Environnements Naturels, Anthropiques et Archéologiques - EA 3795 (GEGENAA), SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Nantes (UN)-Mines Nantes (Mines Nantes), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Limoges ( UNILIM ), Laboratoire SUBATECH Nantes ( SUBATECH ), Mines Nantes ( Mines Nantes ) -Université de Nantes ( UN ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Groupe d'Étude sur les Géomatériaux et Environnements Naturels, Anthropiques et Archéologiques - EA 3795 ( GEGENAA ), Université de Reims Champagne-Ardenne ( URCA ) -Institut national de recherches archéologiques préventives ( Inrap ) -SFR Condorcet, Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Centre National de la Recherche Scientifique ( CNRS ), Cytokines, hématopoïèse et réponse immune ( CHRI ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Oncology, Male, MESH : Retrospective Studies, MESH : Recurrence, MESH : Antineoplastic Combined Chemotherapy Protocols, MESH : Aged, MESH: Western World, Extranodal Disease, chemistry.chemical_compound, 0302 clinical medicine, MESH: Aged, 80 and over, Aggressive NK-cell leukemia, Recurrence, MESH : Western World, Antineoplastic Combined Chemotherapy Protocols, T-cell lymphoma, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Asparaginase, Disseminated disease, MESH : Female, MESH: Lymphoma, Extranodal NK-T-Cell, MESH: Treatment Outcome, Aged, 80 and over, MESH: Aged, 0303 health sciences, Leukemia, MESH: Middle Aged, MESH : Lymphoma, Extranodal NK-T-Cell, Hematology, MESH : Adult, Middle Aged, MESH: Drug Resistance, Neoplasm, 3. Good health, Lymphoma, Extranodal NK-T-Cell, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH : Drug Resistance, Neoplasm, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Adult, medicine.medical_specialty, Asparaginase, MESH : Male, MESH : Treatment Outcome, 03 medical and health sciences, Internal medicine, MESH : Asparaginase, MESH: Leukemia, medicine, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, 030304 developmental biology, Aged, Retrospective Studies, MESH: Humans, business.industry, MESH : Humans, MESH : Leukemia, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Male, Lymphoma, MESH: Recurrence, Regimen, chemistry, Drug Resistance, Neoplasm, Immunology, Western World, business, MESH: Female
Abstract: International audience; BACKGROUND: Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are highly aggressive diseases with a poor outcome. PATIENTS AND METHODS: We report a multicentric French retrospective study of 15 patients with relapsed, refractory, or disseminated disease, treated with L-asparaginase-containing regimens in seven French centers. Thirteen patients were in relapse and/or refractory and 10 patients were at stage IV. RESULTS: All but two of the patients had an objective response to L-asparaginase-based treatment. Seven patients reached complete remission and only two relapsed. CONCLUSION: These data, although retrospective, confirm the excellent activity of L-asparaginase-containing regimens in refractory extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia. Therefore, L-asparaginase-based regimen should be considered as a salvage treatment, especially for patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia should be tested in prospective trials.
Published: 2009
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8. Infections in 252 patients with common variable immunodeficiency

Author: Oksenhendler, Eric, Gérard, Laurence, Fieschi, Claire, Malphettes, Marion, Mouillot, Gael, Jaussaud, Roland, Viallard, Jean-François, Gardembas, Martine, Galicier, Lionel, Schleinitz, Nicolas, Suarez, Felipe, Soulas-Sprauel, Pauline, Hachulla, Eric, Jaccard, Arnaud, Gardeur, Anaelle, Théodorou, Ioannis, Rabian, Claire, Debré, Patrice, Renseigné, Non, Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'immunologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Médecine Interne, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Immunologie cellulaire et tissulaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Claude Huriez, Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service d'Immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Immunologie et chimie thérapeutiques ( ICT ), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique ( CNRS ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]
Subjects: Male, MESH : Common Variable Immunodeficiency, Time Factors, MESH : Prevalence, MESH : Aged, MESH : Respiratory Tract Infections, MESH : Diarrhea, MESH: Common Variable Immunodeficiency, Hypogammaglobulinemia, 0302 clinical medicine, MESH: Aged, 80 and over, MESH : Child, MESH: Child, Prevalence, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH : Anti-Bacterial Agents, Sinusitis, Child, Respiratory Tract Infections, Aged, 80 and over, MESH: Immunoglobulin G, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Respiratory tract infections, Age Factors, MESH : Adult, Middle Aged, 3. Good health, Anti-Bacterial Agents, MESH: Diarrhea, Infectious Diseases, MESH: Communicable Diseases, Bronchitis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Time Factors, Microbiology (medical), Adult, Diarrhea, medicine.medical_specialty, MESH: Pneumonia, MESH : Immunoglobulin G, Adolescent, MESH : Male, Communicable Diseases, 03 medical and health sciences, MESH : Adolescent, Internal medicine, MESH: Anti-Bacterial Agents, medicine, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, MESH: Prevalence, 030304 developmental biology, Aged, MESH: Adolescent, MESH: Age Factors, Bronchiectasis, MESH: Humans, business.industry, MESH : Pneumonia, MESH : Communicable Diseases, Common variable immunodeficiency, MESH : Humans, MESH: Time Factors, MESH: Adult, Pneumonia, medicine.disease, MESH: Male, Upper respiratory tract infection, Common Variable Immunodeficiency, Immunoglobulin G, Immunology, MESH: Respiratory Tract Infections, MESH : Age Factors, business, MESH: Female, 030215 immunology
Abstract: International audience; BACKGROUND: Common variable immunodeficiency is characterized by recurrent infections and defective immunoglobulin production. METHODS: The DEFI French national study prospectively enrolled adult patients with primary hypogammaglobulinemia. Clinical events before inclusion were retrospectively analyzed at that time. RESULTS: From April 2004 through April 2007, 341 patients were enrolled, 252 of whom had received a diagnosis of common variable immunodeficiency; of those, 110 were male, 142 were female, and 228 were white. The median age at first symptoms was 19 years. The median age at common variable immunodeficiency diagnosis was 33.9 years. The median delay for diagnosis was 15.6 years for the 138 patients with initial symptoms before 1990 and 2.9 years for the 114 patients with initial symptoms from 1990 to the time of the study. The most frequent initial symptoms were upper respiratory tract infections: bronchitis (in 38% of patients), sinusitis (36%), pneumonia (31%), and/or bronchiectasis (14%). Overall, 240 patients had respiratory symptoms. Pneumonia was reported in 147 patients; Streptococcus pneumoniae and Haemophilus influenzae were documented in 46 and 17 cases, respectively. Recurrent or chronic diarrhea was reported in 118 patients. Giardia (35 cases), Salmonella (19), and Campylobacter (19) infections were more frequent in patients with undetectable serum immunoglobulin A (P
Published: 2008
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9. The clinical spectrum of IgM-related amyloidosis: a French nationwide retrospective study of 72 patients

Author: Richard Delarue, Mathilde Hunault-Berger, Olivier Tournilhac, Arnaud Jaccard, Philippe Rodon, Pierre Morel, Marc Bernard, Arnaud Hot, Mohamed Hamidou, Benjamin Terrier, Fadi Fakhouri, Olivier Gisserot, Jean-Paul Fermand, Bernard Grosbois, Caroline Elie, Jacques Dantal, Véronique Leblond, Valérie Coiteux, Jean-Luc Harousseau, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération des maladies infectieuses, CHU Clermont-Ferrand, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Institut de transplantation et de recherche en transplantation (ITERT), Laboratoire Hubert Curien [Saint Etienne] (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Laboratoire de physique des milieux ionisés et applications (LPMIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de médecine interne, Physique des milieux ionisés et applications (LPMIA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -ITUN, Institut de transplantation et de recherche en transplantation ( ITERT ), Laboratoire Hubert Curien [Saint Etienne] ( LHC ), Institut d'Optique Graduate School ( IOGS ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ), Physique des milieux ionisés et applications ( LPMIA ), Université Henri Poincaré - Nancy 1 ( UHP ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP)
Subjects: Male, Pathology, MESH: Remission Induction, MESH : Retrospective Studies, medicine.medical_treatment, MESH : Aged, MESH : Alkylating Agents, MESH: Antigens, CD20, Hematopoietic stem cell transplantation, Gastroenterology, MESH: Antibodies, Monoclonal, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Treatment Outcome, Aged, 80 and over, MESH: Middle Aged, MESH: Heart Diseases, Amyloidosis, MESH: Immunologic Factors, Remission Induction, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, General Medicine, MESH: Immunoglobulin M, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, MESH : Paraproteinemias, Rituximab, medicine.medical_specialty, Alkylating Agents, MESH: Serum Albumin, 03 medical and health sciences, MESH: Lymphatic Diseases, MESH : Antigens, CD20, MESH : Hematopoietic Stem Cell Transplantation, AL amyloidosis, Humans, Immunologic Factors, MESH : Middle Aged, MESH : Aged, 80 and over, Lymphatic Diseases, Aged, Retrospective Studies, MESH: Humans, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH : Amyloidosis, Complication, MESH: Female, Lung Diseases, Paraproteinemias, Antibodies, Monoclonal, Murine-Derived, MESH: Lung Diseases, MESH: Paraproteinemias, MESH: Aged, 80 and over, MESH : Purines, MESH : Female, Prospective cohort study, MESH: Aged, MESH : Lung Diseases, MESH : Lymphatic Diseases, MESH: Purines, Middle Aged, MESH : Adult, MESH : Survival Rate, Hematologic Response, MESH: Alkylating Agents, Treatment Outcome, MESH : Antibodies, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, medicine.drug, Adult, Heart Diseases, MESH: Survival Rate, MESH : Immunoglobulin M, MESH : Male, MESH : Treatment Outcome, MESH : Immunologic Factors, MESH : Serum Albumin, Internal medicine, medicine, MESH: Amyloidosis, MESH : France, Serum Albumin, MESH: Hematopoietic Stem Cell Transplantation, MESH : Remission Induction, business.industry, Retrospective cohort study, MESH : Heart Diseases, Antigens, CD20, MESH: Male, MESH: France, Immunoglobulin M, Purines, business, 030215 immunology
Abstract: International audience; Immunoglobulin M (IgM)-related amyloidosis remains a rare and little-known complication of monoclonal IgM-associated disorders. We sought to determine the clinical and laboratory presentation, response to treatment, and outcome of patients with IgM-related amyloidosis in the era of new therapeutic approaches. We conducted a retrospective study in 29 French centers to identify patients with monoclonal IgM and biopsy-proven amyloidosis; we reviewed patients' records and collected relevant clinical and laboratory data. We identified 72 patients with IgM-related amyloidosis. Systemic primary amyloidosis (AL) was present in 64, peritumoral AL in 5, and systemic secondary amyloidosis (AA) in 3 patients. A peculiar pattern of relatively frequent lymph node (31%) and lung (17%) involvement was noted in patients with systemic AL amyloidosis. Response to alkylating agents was poor, with a hematologic response in 37%, a complete remission in 0%, and an organ response in 21%. Response to hematopoietic stem cell transplantation showed a hematologic response in 100% with complete remission in 75% and an organ response in 75%. Purine analogs and rituximab induced a hematologic response in 73% and 60%, respectively, with complete remission in 9% and 0% and an organ response in 55% and 0%, respectively. In multivariate analysis, prognostic factors for survival were serum albumin level < or =3.5 g/dL (p = 0.018) and heart involvement (p = 0.0034). Further prospective studies are needed in patients with IgM-related amyloidosis, with special emphasis on treatment options: hematopoietic stem cell transplantation and purine analogs could represent the most effective therapies. The identification of adverse prognostic factors of survival could be useful for those managing and making treatment decisions for these patients.
Published: 2008
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10. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis

Author: Olivier Hermine, Pierre Ronco, Fabrice Quet, Philippe Moreau, Michel Cogné, Bruno Royer, Bouchra Asli, Bernard Grosbois, Christian Recher, Fabrice Jardin, Jean-Charles Piette, Xavier Leleu, Lofti Benboubker, Véronique Leblond, Bruno Lioure, Arnaud Jaccard, Franck Bridoux, Jean-Paul Fermand, Jérôme Jaubert, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Hématologie thérapie cellulaire, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Limoges (UNILIM), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), CHRU Tours, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université de Limoges ( UNILIM )
Subjects: Melphalan, Male, medicine.medical_specialty, medicine.medical_treatment, Urology, Hematopoietic stem cell transplantation, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Dexamethasone, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, AL amyloidosis, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, Aged, Chemotherapy, business.industry, Amyloidosis, Hematopoietic Stem Cell Transplantation, General Medicine, Middle Aged, Myeloablative Agonists, medicine.disease, Combined Modality Therapy, Nitrogen mustard, 3. Good health, Surgery, Transplantation, chemistry, 030220 oncology & carcinogenesis, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, Immunoglobulin Light Chains, business, medicine.drug
Abstract: http://content.nejm.org/cgi/content/abstract/357/11/1083; International audience; High-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation has been reported to provide higher response rates and better overall survival than standard chemotherapy in immunoglobulin-light-chain (AL) amyloidosis, but these two strategies have not been compared in a randomized study. METHODS: We conducted a randomized trial comparing high-dose intravenous melphalan followed by autologous hematopoietic stem-cell rescue with standard-dose melphalan plus high-dose dexamethasone in patients with AL amyloidosis. Patients (age range, 18 to 70 years) with newly diagnosed AL amyloidosis were randomly assigned to receive intravenous high-dose melphalan plus autologous stem cells or oral melphalan plus oral high-dose dexamethasone. RESULTS: Fifty patients were enrolled in each group. The results were analyzed on an intention-to-treat basis, with overall survival as the primary end point. After a median follow-up of 3 years, the estimated median overall survival was 22.2 months in the group assigned to receive high-dose melphalan and 56.9 months in the group assigned to receive melphalan plus high-dose dexamethasone (P=0.04). Among patients with high-risk disease, overall survival was similar in the two groups. Among patients with low-risk disease, there was a nonsignificant difference between the two groups in overall survival at 3 years (58% in the group assigned to receive high-dose melphalan vs. 80% in the group assigned to receive melphalan plus high-dose dexamethasone; P=0.13). CONCLUSIONS: The outcome of treatment of AL amyloidosis with high-dose melphalan plus autologous stem-cell rescue was not superior to the outcome with standard-dose melphalan plus dexamethasone. (ClinicalTrials.gov number, NCT00344526 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.
Published: 2007

11. Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study

Author: Lucienne Chatenoud, Loïc Bergougnoux, Augustin Ferrant, Franck Morschhauser, Gérard Socié, Raoul Herbrecht, Peter Vandenberghe, Samira Fafi-Kremer, Noel Milpied, Gilles Salles, Arnaud Jaccard, Véronique Leblond, Alain Fischer, Philippe Lang, Anne Moreau, Walter Feremans, Sylvain Choquet, Patrice Morand, Olivier Hermine, Eric Oksenhendler, Thierry Lamy, Fritz Offner, Etienne Vilmer, Anne-Marie Stoppa, Yvon Lebranchu, Nathalie Berriot-Varoqueaux, Marie-Noëlle Peraldi, Jeanne Luce Garnier, Unité d'hématologie et de transplantation, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Immunologie et d'Hématologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP), Biophysique, Médecine Nucléaire et Technologies Médicales ( EA 1049 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Département de pathologie, Hospices Civils de Lyon ( HCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon, Registre National des Hémopathies malignes de l'Enfant ( RNHE ), Institut de Veille Sanitaire (INVS)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service de néphrologie et immunologie clinique, Hôpital Bretonneau-Université de Tours-CHRU Tours, Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Interaction virus-hôte et maladies du foie, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Virologie moléculaire et structurale, CHU Grenoble, Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biophysique, Médecine Nucléaire et Technologies Médicales (EA 1049), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Registre National des Hémopathies malignes de l'Enfant (RNHE), Institut de Veille Sanitaire (INVS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Bretonneau-Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de virologie moléculaire et structurale (LVMS), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), and Université de Tours (UT)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau
Subjects: Male, MESH: Remission Induction, medicine.medical_treatment, MESH : Prospective Studies, MESH : Aged, Phases of clinical research, Biochemistry, Gastroenterology, Organ transplantation, MESH: Antibodies, Monoclonal, MESH : Organ Transplantation, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, MESH: Lymphoproliferative Disorders, hemic and lymphatic diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Prospective Studies, Prospective cohort study, MESH: Aged, B-Lymphocytes, MESH: Middle Aged, MESH : Lymphoproliferative Disorders, MESH: Hydro-Lyases, Remission Induction, Antibodies, Monoclonal, Immunosuppression, Hematology, MESH : Adult, Middle Aged, 3. Good health, MESH : Antineoplastic Agents, surgical procedures, operative, 030220 oncology & carcinogenesis, MESH : Antibodies, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Disease-Free Survival, Rituximab, Female, medicine.drug, Adult, medicine.medical_specialty, Adolescent, MESH : Male, Immunology, Lymphoproliferative disorders, MESH: Organ Transplantation, MESH : Hydro-Lyases, Antineoplastic Agents, Disease-Free Survival, MESH : B-Lymphocytes, 03 medical and health sciences, Internal medicine, MESH: B-Lymphocytes, MESH : Adolescent, medicine, Humans, MESH : Middle Aged, Hydro-Lyases, Aged, MESH: Adolescent, MESH : Remission Induction, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, Cell Biology, Organ Transplantation, medicine.disease, MESH: Male, MESH: Prospective Studies, Lymphoproliferative Disorders, Surgery, Transplantation, Clinical trial, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, business, MESH: Female, 030215 immunology
Abstract: International audience; B-cell posttransplantation lymphoproliferative disorder (B-PTLD) is a rare but severe complication of transplantation, with no consensus on best treatment practice. This prospective trial, the first to test a treatment for PTLD, was designed to evaluate the efficacy and safety of rituximab in patients with B-PTLD after solid organ transplantation (SOT). Forty-six patients were included and 43 patients were analyzed. Patients were eligible if they had untreated B-PTLD that was not responding to tapering of immunosuppression. Treatment consisted of 4 weekly injections of rituximab at 375 mg/m2. At day (d) 80, 37 (86%) patients were alive, and the response rate was 44.2%, including 12 complete response/unconfirmed complete response (CR/CRu). The only factor predictive of a response at d80 was a normal lactate dehydrogenase level (P = .007, odds ratio [OR] = 6.9). At d360, responses were maintained in 68% of patients, and 56% of patients were alive. The overall survival rate at 1 year was 67%. We conclude that rituximab is effective and safe in PTLD, with stable responses at 1 year. The response rate and overall survival might be improved by combining rituximab with other treatments.
Published: 2005
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12. The renal epidemiology and information network (REIN): a new registry for end-stage renal disease in France

Author: Hubert Isnard, Cécile Couchoud, Jean-Claude Aldigier, Michel Labeeuw, Hervé Maheut, Michèle Kessler, François de Cornelissen, Christian Jacquelinet, Bénédicte Stengel, Paul Landais, Véronique Joyeux, Christian Dabot, Registre REIN, Agence de la biomédecine [Saint-Denis la Plaine], Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Male, MESH: Registries, medicine.medical_treatment, 030232 urology & nephrology, MESH : Aged, 030204 cardiovascular system & hematology, MESH : Child, Preschool, urologic and male genital diseases, 0302 clinical medicine, MESH: Aged, 80 and over, MESH : Child, MESH: Child, Epidemiology, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Registries, Child, MESH: Aged, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, MESH : Adult, Middle Aged, 3. Good health, Nephrology, MESH: Kidney Failure, Chronic, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Hemodialysis, France, Adult, medicine.medical_specialty, Adolescent, MESH : Male, Population, MESH : Kidney Failure, Chronic, Peritoneal dialysis, End stage renal disease, 03 medical and health sciences, Internal medicine, MESH : Adolescent, medicine, Humans, MESH : Middle Aged, Renal replacement therapy, Intensive care medicine, education, MESH : Aged, 80 and over, MESH : France, Dialysis, Aged, MESH: Adolescent, Transplantation, MESH: Humans, business.industry, MESH: Child, Preschool, MESH : Humans, MESH: Adult, medicine.disease, MESH: Male, MESH: France, Kidney Failure, Chronic, business, MESH: Female, MESH : Registries, Kidney disease
Abstract: International audience; The French Renal Epidemiology and Information Network (REIN) registry began in 2002 to provide a tool for public health decision support, evaluation and research related to renal replacement therapies (RRT) for end-stage renal disease (ESRD). It relies on a network of nephrologists, epidemiologists, patients and public health representatives, coordinated regionally and nationally. Continuous registration covers all dialysis and transplanted patients. In 2003, 2070 patients started RRT, 7854 were on dialysis and 7294 lived with a functioning graft in seven regions (with a population of 16.5 million people). The overall crude annual incidence rate of RRT for ESRD was 123 per million population (p.m.p.) with significant differences in age-adjusted rates across regions, from 84 [95% confidence interval (CI): 74-94] to 155 [138-172] p.m.p. The principal causes of ESRD were hypertension (21%) and diabetic (20%) nephropathies. Initial treatment for ESRD was peritoneal dialysis for 15% of patients and a pre-emptive graft for 3%. The one-year survival rate was 81% [79-83] in the cohort of 2002-2003 incident patients. As of December 31, 2003, the overall crude prevalence was 898 [884-913] p.m.p, with 5% of patients receiving peritoneal dialysis, 47% on haemodialysis and 48% with a functioning graft. The experience in these seven regions over these two years clearly shows the feasibility of the REIN registry, which is progressively expanding to cover the entire country.
Published: 2005
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13. Platelet-activating factor does not stimulate cAMP formation from immature forms of freshly isolated leukaemic blasts

Author: Yves Denizot, Magali Donnard, Jean Faucher, Pascal Turlure, Dominique Bordessoule, Véronique Truffinet, Franck Trimoreau, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Cancer Research, CD34, PAF receptor, chemistry.chemical_compound, Cyclic AMP, MESH : Precursor Cell Lymphoblastic Leukemia-Lymphoma, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, CAMP formation, MESH: Cyclic AMP, MESH: Middle Aged, blast cells, MESH : Cyclic AMP, Cell Differentiation, Hematology, respiratory system, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Cell biology, Haematopoiesis, Leukemia, Myeloid, Acute, Oncology, [SDV.IMM]Life Sciences [q-bio]/Immunology, lipids (amino acids, peptides, and proteins), Female, MESH: Leukemia, Myeloid, Acute, MESH : Cell Differentiation, Intracellular, MESH: Cell Differentiation, MESH: Cell Line, Tumor, NLM, MESH : Male, MESH : Leukemia, Myeloid, Acute, Phospholipid, Biology, Mediator, Precursor cell, Cell Line, Tumor, Humans, MESH : Middle Aged, Platelet Activating Factor, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Platelet Activating Factor, MESH: Humans, Platelet-activating factor, MESH : Cell Line, Tumor, MESH : Humans, MESH: Male, chemistry, MESH : Platelet Activating Factor, MESH: Female
Abstract: To the Editor,PAF is a phospholipid mediator that sparks off awide range of immunoregulatory actions on maturehaematopoietic cells [1]. Intracellular and nuclearPAF-receptors (PAF-R) are reported [2–5]. Theybelong to the G-protein-coupled family. Studieshighlight the presence of PAF-R transcripts innormal haematopoietic CD34
Published: 2005
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14. Detection of Functional Platelet-Activating Factor Receptors on Leukemic B Cells of Chronic Lymphocytic Leukemic Patients

Author: Yves Denizot, Dominique Bordessoule, Laurence Guglielmi, Arnaud Jaccard, Magali Donnard, Franck Trimoreau, Jean-Luc Faucher, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), and Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Male, Cancer Research, NLM, Nuclear Envelope, Cell, Proliferation, Il-4, Platelet Membrane Glycoproteins, Lymphocyte Activation, Receptors, G-Protein-Coupled, chemistry.chemical_compound, Paf Receptors, In vivo, Transforming Growth Factor beta, PAF receptors, medicine, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Camp, Receptor, B cell, Interleukin 4, Aged, B-Lymphocytes, Platelet-activating factor, Chronic B Cell Leukemia, Chemistry, Cell Membrane, Hematology, Leukemia, Lymphocytic, Chronic, B-Cell, medicine.anatomical_structure, Oncology, Case-Control Studies, Immunology, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, lipids (amino acids, peptides, and proteins), Interleukin-4
Abstract: Although platelet-activating factor receptors (PAF-R) are reported on normal B cells, few results are available concerning leukemic ones. We demonstrated functional PAF-R on cell and nuclear surfaces of leukemic B cells of chronic lymphocytic leukemic (CLL) patients. Analysis of 102 patients revealed dramatic differences for their membrane PAF-R expression, a result that might be related to their plasma IL-4 levels. In the light of the potent immunoregulatory role of PAF on B cell physiology, it is suggested that the presence or absence of PAF-R on leukemic B cells may profoundly affect their in vivo behavior.
Published: 2005
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15. Platelet-activating factor and normal or leukaemic haematopoiesis

Author: Laurence Guglielmi, Yves Denizot, Franck Trimoreau, Magali Donnard, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), and Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Signal Transduction, Cancer Research, B Cells, MESH : Receptors, Cell Surface, MESH: Hematopoiesis, Paf Receptor, MESH: Receptors, G-Protein-Coupled, Receptors, G-Protein-Coupled, chemistry.chemical_compound, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Receptor, MESH: Receptors, Cell Surface, B-Lymphocytes, Leukemia, Hematology, Leukaemic Diseases, Haematopoiesis, medicine.anatomical_structure, Oncology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Receptors, G-Protein-Coupled, lipids (amino acids, peptides, and proteins), Signal Transduction, Stromal cell, NLM, Receptors, Cell Surface, Blast Cells, Platelet Membrane Glycoproteins, Biology, MESH : B-Lymphocytes, Precursor cell, MESH: B-Lymphocytes, MESH: Leukemia, medicine, Humans, Progenitor cell, Platelet Activating Factor, B cell, MESH : Signal Transduction, MESH: Platelet Activating Factor, MESH: Humans, Platelet-activating factor, MESH : Humans, MESH : Leukemia, MESH: Platelet Membrane Glycoproteins, Hematopoiesis, MESH : Hematopoiesis, chemistry, MESH : Platelet Activating Factor, Immunology, Cancer research, Bone marrow, Platelet-activating Factor, MESH : Platelet Membrane Glycoproteins
Abstract: Platelet-activating factor (PAF), a phospholipid mediator with a wide range of actions on mature leukocytes, acts directly during early human haematopoiesis by affecting the growth of haematopoietic progenitors and indirectly, by modulating cytokine synthesis by bone marrow stromal cells. At this time, its role during leukaemic diseases remains speculative. The lack of membrane PAF receptor (PAF-R) on leukaemic blasts suggest that this receptor represents a marker of mature cells and its membrane induction a consequence of cell maturation. While the couple PAF/PAF-R has been largely studied using B cell lines, few results are available using B cells of patients with haematopoietic malignancies casting some doubts concerning the potential role (if any) of this molecule during leukaemic diseases.
Published: 2003
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16. Presence of membrane platelet-activating factor receptors on B cells of chronic B cell leukaemia patients

Author: Dominique Bordessoule, Magali Donnard, Franck Trimoreau, Arnaud Jaccard, Yves Denizot, Laurence Guglielmi, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Cancer Research, NLM, MESH : Male, MESH : Aged, MESH : Receptors, Cell Surface, Receptors, Cell Surface, MESH: Receptors, G-Protein-Coupled, Platelet Membrane Glycoproteins, Receptors, G-Protein-Coupled, MESH : B-Lymphocytes, chemistry.chemical_compound, MESH: B-Lymphocytes, medicine, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH : Middle Aged, Receptor, MESH: Leukemia, Lymphocytic, Chronic, B-Cell, B cell, MESH: Receptors, Cell Surface, Aged, MESH: Aged, B-Lymphocytes, MESH: Humans, MESH: Middle Aged, Platelet-activating factor, Chemistry, MESH : Humans, MESH: Platelet Membrane Glycoproteins, Hematology, Middle Aged, MESH : Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Molecular biology, MESH: Male, Membrane, medicine.anatomical_structure, Oncology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Receptors, G-Protein-Coupled, MESH: Female, MESH : Platelet Membrane Glycoproteins
Published: 2003
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17. Heavy Chain Fibrillary Glomerulonephritis: A Case Report

Author: Angela Dispenzieri, Mariam P. Alexander, Frank Bridoux, Vincent Javaugue, Alexia Rinsant, Ellen D. McPhail, Sihem Kaaki, Jonathan J. Hogan, Sébastien Bender, Emilie Pinault, Surendra Dasari, Samar M. Said, Guy Touchard, Nelson Leung, Christophe Sirac, Samih H. Nasr, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Unité de Génétique Moléculaire Animale (UMR GMA), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), Division of Biomedical Statistics and Informatics, Mayo Clinic, Division of Hematology, Mayo Clinic Rochester, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Unité de Génétique Moléculaire Animale (UGMA)
Subjects: Male, Pathology, medicine.medical_specialty, Paraproteinemias, 030232 urology & nephrology, Immunoglobulin light chain, Immunoglobulin G, 03 medical and health sciences, Fatal Outcome, Glomerulonephritis, 0302 clinical medicine, Biopsy, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Kidney, medicine.diagnostic_test, biology, business.industry, Amyloidosis, Fibrillary Glomerulonephritis, Middle Aged, medicine.disease, 3. Good health, medicine.anatomical_structure, Nephrology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin heavy chain, Immunoglobulin Heavy Chains, business, Kidney disease
Abstract: Heavy chain amyloidosis and heavy chain deposition disease are the only known kidney diseases caused by the deposition of truncated immunoglobulin heavy chains. Fibrillary glomerulonephritis typically results from deposition of DNAJB9 (DnaJ heat shock protein family [Hsp40] member B9) and polytypic immunoglobulin G (IgG). We describe a patient with monoclonal gammopathy (IgG with λ light chain) who developed DNAJB9-negative fibrillary glomerulonephritis leading to end-stage kidney disease, with recurrence in 2 kidney allografts. Pre- and postmortem examination showed glomerular deposition of Congo red-negative fibrillar material that was determined to be immunoglobulin heavy chain. We propose the term "heavy chain fibrillary glomerulonephritis" to describe this lesion, which appears to be a rare kidney complication of monoclonal gammopathy. The diagnosis should be suspected when the kidney biopsy shows fibrillary glomerulonephritis with negative staining for immunoglobulin light chains and DNAJB9; the diagnosis can be confirmed using immunochemical and molecular studies.
Published: 2019
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18. Mesangial deposition can strongly involve innate-like iga molecules lacking affinity maturation

Author: Michel Cogné, Yolla Makhour, Batoul Wehbi, Jeanne Moreau, Anne Druilhe, Christelle Oblet, Arnaud Huard, Etienne Cogné, Marjolein van Egmond, Jean-Claude Aldigier, François Boyer, Bassam Badran, François Paraf, Molecular cell biology and Immunology, Surgery, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, AII - Inflammatory diseases, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Croissance et Signalisation [Paris], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Limoges (UNILIM), Laboratory of Experimental Hematology, Université libre de Bruxelles (ULB)-Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB), Laboratoire d'Immunologie et Immunopathologie [CHU Poitiers] (CNRS URA 1172), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Université Libre de Bruxelles [Bruxelles] (ULB)-Bordet Institute, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Glycosylation, Antibody Affinity, 030232 urology & nephrology, Inflammation, Receptors, Fc, urologic and male genital diseases, Nephropathy, Affinity maturation, Pathogenesis, Mice, 03 medical and health sciences, 0302 clinical medicine, Antigens, CD, Cytidine Deaminase, Up Front Matters, medicine, Animals, Humans, Receptor, Complement Activation, ComputingMilieux_MISCELLANEOUS, biology, Chemistry, Glomerulonephritis, IGA, General Medicine, medicine.disease, Complement system, Glomerular Mesangium, Immunoglobulin A, Proteinuria, 030104 developmental biology, Basic Research, Nephrology, Mesangium, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, Antibody
Abstract: BACKGROUND: IgA nephropathy (IgAN) often follows infections and features IgA mesangial deposition. Polymeric IgA deposits in the mesangium seem to have varied pathogenic potential, but understanding their pathogenicity remains a challenge. Most mesangial IgA1 in human IgAN has a hypogalactosylated hinge region, but it is unclear whether this is required for IgA deposition. Another important question is the role of adaptive IgA responses and high-affinity mature IgA antibodies and whether low-affinity IgA produced by innate-like B cells might also yield mesangial deposits. METHODS: To explore the effects of specific qualitative variations in IgA and whether altered affinity maturation can influence IgA mesangial deposition and activate complement, we used several transgenic human IgA1-producing models with IgA deposition, including one lacking the DNA-editing enzyme activation-induced cytidine deaminase (AID), which is required in affinity maturation. Also, to explore the potential role of the IgA receptor CD89 in glomerular inflammation, we used a model that expresses CD89 in a pattern observed in humans. RESULTS: We found that human IgA induced glomerular damage independent of CD89. When comparing mice able to produce high-affinity IgA antibodies with mice lacking AID-enabled Ig affinity maturation, we found that IgA deposition and complement activation significantly increased and led to IgAN pathogenesis, although without significant proteinuria or hematuria. We also observed that hinge hypoglycosylation was not mandatory for IgA deposition. CONCLUSIONS: In a mouse model of IgAN, compared with high-affinity IgA, low-affinity innate-like IgA, formed in the absence of normal antigen-driven maturation, was more readily involved in IgA glomerular deposition with pathogenic effects.
Published: 2019
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19. PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice

Author: Guillaume Chemin, Sylvie Hébrard, Chloé Oudinet, Ngoc Sa Nguyen Huu, Pierre Brousset, Stéphanie Lagarde, Laura Jamrog, Vincent Fregona, Cyril Broccardo, Bastien Gerby, Cathy Quelen, Eric Delabesse, Marina Bousquet, Stéphane J. C. Mancini, Naïs Prade, Nelly Rouquié, Charlotte Cresson, Marlène Pasquet, Lucie Coster, Ahmed Amine Khamlichi, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Hématologie pédiatrique, CHU Toulouse [Toulouse], Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), LIttoral ENvironnement et Sociétés - UMR 7266 (LIENSs), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Tumor suppressor gene, Oncogene Proteins, Fusion, Transgene, [SDV]Life Sciences [q-bio], Chromosomal translocation, Mice, Transgenic, Protein Tyrosine Phosphatase, Non-Receptor Type 11, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, medicine, Animals, Gene Knock-In Techniques, Gene, ComputingMilieux_MISCELLANEOUS, B-Lymphocytes, Multidisciplinary, Cell growth, Gene Expression Regulation, Leukemic, PAX5 Transcription Factor, Janus Kinase 3, Neoplasms, Experimental, Biological Sciences, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Fusion protein, Elastin, Leukemia, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Cancer research, PAX5
Abstract: International audience; PAX5 is a well-known haploinsufficient tumor suppressor gene in human B-cell precursor acute lymphoblastic leukemia (B-ALL) and is involved in various chromosomal translocations that fuse a part of PAX5 with other partners. However, the role of PAX5 fusion proteins in BALL initiation and transformation is ill-known. We previously reported a new recurrent t(7;9)(q11;p13) chromosomal translocation in human BALL that juxtaposed PAX5 to the coding sequence of elastin (ELN). To study the function of the resulting PAX5-ELN fusion protein in BALL development, we generated a knockin mouse model in which the PAX5-ELN transgene is expressed specifically in B cells. PAX5-ELN-expressing mice efficiently developed BALL with an incidence of 80%. Leukemic transformation was associated with recurrent secondary mutations on Ptpn11, Kras, Pax5, and Jak3 genes affecting key signaling pathways required for cell proliferation. Our functional studies demonstrate that PAX5-ELN affected B-cell development in vitro and in vivo featuring an aberrant expansion of the pro-B cell compartment at the preleukemic stage. Finally, our molecular and computational approaches identified PAX5-ELN-regulated gene candidates that establish the molecular bases of the pre-leukemic state to drive BALL initiation. Hence, our study provides a new in vivo model of human BALL and strongly implicates PAX5 fusion proteins as potent oncoproteins in leukemia development.
Published: 2018
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20. Design and Synthesis of Tubulin and Histone Deacetylase Inhibitor Based on iso -Combretastatin A-4

Author: François Saller, Cyril Bauvais, Hsin-Ping Lin, Hazar Al-Mouhammad, Guillaume Bollot, Martin Souce, Diana Lamaa, Olivier Pamlard, Athena Kasselouri, Abdallah Hamze, Joëlle Dubois, Lena Zig, Mehdi Ouaissi, Delphine Borgel, Jean Feuillard, Hélène Levaique, Chantal Jayat-Vignoles, Mouad Alami, Jérôme Bignon, Karim Benihoud, Molécules bioactives, conception, isolement et synthèse (MBCIS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Physico-Chimique, Centre National de la Recherche Scientifique (CNRS), Synsight, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Chimie Analytique Pharmaceutique - Faculté de Pharmacie (Lip(Sys)2), Université Paris-Sud - Paris 11 (UP11), Groupe de Chimie Analytique de Paris-Sud, Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Université Paris-Sud - Paris 11 (UP11)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Hematology [Paris], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), and Université Paris-Seine-Université Paris-Seine-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, medicine.drug_class, Protein Conformation, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, Chemistry Techniques, Synthetic, 01 natural sciences, Histone Deacetylases, 03 medical and health sciences, chemistry.chemical_compound, Tubulin, Drug Discovery, Stilbenes, medicine, Tubulin polymerization, Humans, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, Combretastatin A-4, biology, 010405 organic chemistry, Drug discovery, Histone deacetylase inhibitor, HDAC8, HCT116 Cells, 0104 chemical sciences, 3. Good health, Histone Deacetylase Inhibitors, 030104 developmental biology, chemistry, Biochemistry, Drug Design, biology.protein, Molecular Medicine, K562 Cells, Belinostat, K562 cells
Abstract: Designing multitarget drugs have raised considerable interest due to their advantages in the treatment of complex diseases such as cancer. Their design constitutes a challenge in antitumor drug discovery. The present study reports a dual inhibition of tubulin polymerization and HDAC activity. On the basis of 1,1-diarylethylenes ( isoCA-4) and belinostat, a series of hybrid molecules was successfully designed and synthesized. In particular compounds, 5f and 5h were proven to be potent inhibitors of both tubulin polymerization and HDAC8 leading to excellent antiproliferative activity.
Published: 2018
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21. Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome

Author: Imen Chabchoub, Didier Lacombe, Marion Sallée, Phillippe Dolhem, Dominique Durand, Karin Dahan, Pierre Ronco, Eric Rondeau, Sylvie Cloarec, Julien Hogan, Gérard Champion, David Ribes, Hubert Nivet, Laurent Mesnard, Georges Deschênes, Thierry Krummel, Khalil El Karoui, Claire Pouteil Noble, Christine Pietrement, Yahsou Delmas, Olivier Gribouval, Olivia Boyer, Tim Ulinski, N. Mohsin, Patrick Niaudet, Guillaume Dorval, Aurélie Hummel, Vanesa Martinez-Barquero, Mongia Hachicha, Véronique Baudouin, Corinne Antignac, Marie-Josèphe Tête, Michel Fischbach, Paloma Maria Parvex, Hassib Chehade, Rémi Salomon, Brigitte Llanas, Dominique Chauveau, Jacques Dantal, Jean-Pierre Grünfeld, S. Benoit, Nassim Kamar, Loïc de Pontual, Eduardo Machuca, Pierre Cochat, Vincent Guigonis, Maryvonne Hourmant, Zelal Ekinci, Chokri Chouchane, Michel Tsimaratos, Laboratoire des Maladies Rénales Héréditaires, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Molecular bases of hereditary kidney diseases: nephronophthisis and hypodysplasia (Equipe Inserm U1163), Néphropathies héréditaires et rein en développement (UMR_S 983), CHU Necker - Enfants Malades [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hedi Chaker Hospital [Sfax], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Monastir - University of Monastir (UM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Département de Pédiatrie, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institute of Pathology and Genetics, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de néphrologie et pédiatrie générale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre hospitalier de Saint-Quentin, Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Kocaeli Academy for Solidarity, Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Service de Pédiatrie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de néphrologie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Department of Pediatrics, Service de Néphrologie pédiatrique [Hôpital Robert Debré, Paris], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Référence du Sud Ouest des Maladies Rénales Rares, CHU Toulouse [Toulouse]-Hôpital des Enfants, Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sultan Qaboos University (SQU), Service de Néphrologie, Hôpital de Clocheville, Geneva University Hospital (HUG), Centre Hospitalier Universitaire de Reims (CHU Reims)-American Memorial Hospital (Reims), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Tenon [APHP], Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie Pédiatrique [Trousseau], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jean Verdier [AP-HP], CHU Tenon [AP-HP], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Glucocorticoids/therapeutic use, Adult, Male, Nephrotic Syndrome, Adolescent, Nephrotic Syndrome/drug therapy/genetics, 030232 urology & nephrology, Disease, Biology, medicine.disease_cause, HLA-DQ alpha-Chains, 03 medical and health sciences, Genetic Heterogeneity, Young Adult, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], HLA-DQ alpha-Chains/genetics, medicine, Humans, Genetic Predisposition to Disease, Young adult, Preschool, Child, Gene, Glucocorticoids, Exome sequencing, ComputingMilieux_MISCELLANEOUS, Genetics, Mutation, ddc:618, Membrane Glycoproteins, Genetic heterogeneity, Infant, Sequence Analysis, DNA, Membrane Glycoproteins/genetics, Middle Aged, medicine.disease, 3. Good health, DNA/methods, 030104 developmental biology, Nephrology, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Female, Nephrotic syndrome, Sequence Analysis
Abstract: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease. Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort. Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p
Published: 2018
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22. Assessing the environmental impact of pesticide use in banana cropping systems

Author: Magalie Jannoyer, Marc Voltz, Irina Comte, Jean-Baptiste Charlier, Charles Mottes, Philippe Cattan, Céline Gentil, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Fonctionnement écologique et gestion durable des agrosystèmes bananiers et ananas (UR GECO), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Faculté de Médecine Purpan, Direction Générale Déléguée à la Recherche et à la Stratégie (Cirad-Dgdrs), Laboratoire d'étude des Interactions Sol - Agrosystème - Hydrosystème (UMR LISAH), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut de Recherche pour le Développement (IRD [ Madagascar])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)
Subjects: 0106 biological sciences, Pollution, media_common.quotation_subject, Hydrological modelling, F08 - Systèmes et modes de culture, [SDV]Life Sciences [q-bio], H02 - Pesticides, Horticulture, 01 natural sciences, water quality, environmental evaluation, Environmental impact assessment, media_common, 2. Zero hunger, Pollutant, 010401 analytical chemistry, Environmental engineering, pesticides, 15. Life on land, Pesticide, 6. Clean water, 0104 chemical sciences, Geography, 13. Climate action, [SDU]Sciences of the Universe [physics], [SDE]Environmental Sciences, Water quality, musa, Water resource management, Martinique, Cropping, P02 - Pollution, multi-scale assessment, 010606 plant biology & botany
Abstract: International audience; In the French West Indies, high pest pressure on cropping systems has triggered high inputs of pesticides, especially in banana cropping systems. These pesticides then disperse in soil, ground and surface water, threatening ecosystem and human health. Reducing the environmental impact of banana cropping systems in this area requires i) predicting environmental states according to cropping systems evolution, ii) identifying key factors triggering pollution, and iii) proposing measures to reduce impact. Since farmers apply pesticides at the field scale while environmental impacts spring up at the watershed scale, multi-scale environmental impact assessments of pesticide use are required. Therefore, our work focuses on the characterization of i) pollutant input (type of molecule, quantity applied, frequency), ii) pollutant transfers, through hydrological modelling, and iii) environmental state through water quality measurements. Studies carried out at field scale, sub-watershed scale and watershed scale will be presented. They were located in Perou river catchment in Guadeloupe and Galion river catchment in Martinique. Results provide a wide overview of the main hydrological processes involved in pesticides transfers towards rivers in tropical volcanic catchments. However, those studies focused either on chlordecone, an old organochlorine, or cadusafos, a nematicide used 10 years ago in banana cropping systems. Recent measurements performed at the watershed scale showed herbicides applied in sugarcane fields and banana post-harvest fungicides to be among the main pollutants in these rivers. Consequently, long-term and multi-residue monitoring is required to understand the fate of the different molecules applied in fields taking account of cropping systems evolution over time. This will be further performed thanks to the set-up of the Observatory of agricultural-source pollution in the French West Indies (OPALE).
Published: 2018
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23. Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Gilardin, Laurent, Delignat, Sandrine, Peyron, Ivan, Ing, Mathieu, Lone, Yu-Chun, Gangadharan, Bagirath, Michard, Baptiste, Kherabi, Yousra, Sharma, Meenu, Pashov, Anastas, Toutirais, Olivier, Loiseau, Pascale, Veyradier, Agnès, Kaveri, Srini, Maillere, Bernard, Coppo, Paul, Lacroix-Desmazes, Sébastien, Chatillon, Jean-François, Hamieh, Mohamad, Bayeux, Florence, Abasq, Claire, Fauquembergue, Emilie, Drouet, Aurélie, Guisier, Florian, Latouche, Jean-Baptiste, Musette, Philippe, Coignard-Biehler, Hélène, Mahlaoui, Nizar, Pilmis, Benoit, Barlogis, Vincent, Brosselin, Pauline, de Vergnes, Nathalie, Debré, Marianne, Malphettes, Marion, Frange, Pierre, Catherinot, Emilie, Pellier, Isabelle, Durieu, Isabelle, Perlat, Antoinette, Royer, Bruno, Le Quellec, Alain, Jeziorski, Eric, Fischer, Alain, Lortholary, Olivier, Aaron+, Laurent, Adoue, Daniel, Aguilar, Claire, Aladjidi, Nathalie, Alcaïs, Alexandre, Amoura, Zahir, Arlet, Philippe, Armari-Alla, Corinne, Bader-Meunier, Brigitte, Bayart, Sophie, Bienvenu, Boris, Blanche, Stéphane, Bodet, Damien, Bonnotte, Bernard, Borie, Raphael, Boutard, Patrick, Briandet, Claire, Brion, Jean-Paul, Brouard, Jacques, Cohen-Beaussant, Sarah, Costes, Laurence, Couderc, Louis-Jean, Cougoul, Pierre, Courteille, Virginie, de Saint Basile, Geneviève, Devoldere, Catherine, Deville, Anne, Donadieu, Jean, Doré, Eric, Dulieu, Fabienne, Edan, Christine, Entz-Werlé, Natacha, Fieschi, Claire, Forestier, Amandine, Fouyssac, Fanny, Gajdos, Vincent, Galicier, Lionel, Gandemer, Virginie, Gardembas, Martine, Gaud, Catherine, Guillerm, Gaelle, Hachulla, Eric, Hamidou, Mohamed, Hermine, Olivier, Hoarau, Cyrille, Humbert, Sebastien, Jaccard, Arnaud, Jacquot, Serge, Jais, Jean-Philippe, Jaussaud, Roland, Jeandel, Pierre-Yves, Kebaili, Kamila, Korganow, Anne-Sophie, Lambotte, Olivier, Lanternier, Fanny, Larroche, Claire, Lascaux, Anne-Sophie, Le Moigne, Emmanuelle, Le Moing, Vincent, Lebranchu, Yvon, Lecuit, Marc, Lefèvre, Guillaume, Lemal, Richard, Te, Valérie Li Thiao, Marie-Cardine, Aude, Silva, Nicolas Martin, Masseau, Agathe, Massot, Christian, Mazingue, Françoise, Merlin, Etienne, Monlibert, Béatrice, Monpoux, Fabrice, Moshous, Despina, Mouthon, Luc, Munzer, Martine, Neven, Bénédicte, Nove-Josserand, Raphaëlle, Oksenhendler, Eric, Ouachée-Chardin, Marie, Oudot, Caroline, Pagnier, Anne, Pasquali, Jean-Louis, Pasquet, Marlène, Perel, Yves, Picard, Capucine, Piguet, Christophe, Plantaz, Dominique, Provot, Johan, Quartier, Pierre, Rieux-Laucat, Frédéric, Roger, Pierre-Marie, Rohrlich, Pierre-Simon, Rubié, Hervé, Salle, Valéry, Sarrot-Reynauld, Françoise, Servettaz, Amélie, Stephan, Jean-Louis, Schleinitz, Nicolas, Suarez, Felipe, Swiader, Laure, Taque, Sophie, Thomas, Caroline, Tournilhac, Olivier, Thumerelle, Caroline, Tron, François, Viallard, Jean-François, Roux, Clément, Tifratene, K, Socie, G., Galambrun, C., Bertrand, Yves, Rialland, F., Jubert, C, Pochon, C, Paillard, C., Sirvent, A., Nelken, B., Vannier, Jean-Pierre, Freycon, C, Beguin, Y, Raus, N, Yakoub-Agha, I., Mohty, M., Dalle, J-H, Michel, Gérard, Pradier, C., Peffault de Latour, R., Rohrlich, P-S, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Greffes d'Epitheliums et Regulation de l'Activation Lymphocytaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Institut Stephan Angeloff, Réseau International des Instituts Pasteur (RIIP), Immunogénétique humaine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Biologique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'Ingénierie et d'Etudes des Protéines, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'immuno-hématologie pédiatrique [CHU Necker], Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Unité d'Immunologie Hématologie et Rhumatologie Pédiatrique [Necker, Paris], Hôpital Foch [Suresnes], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Interne - Centre Hospitalier Lyon Sud, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], CHU Amiens-Picardie, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital de la Tronche, Département d'Immunologie, hématologie et rhumatologie pédiatriques [Hôpital Necker-Enfants malades - APHP], Hématogoie pédiatrique, hôpital Sud, Laboratoire de Mathématiques Nicolas Oresme (LMNO), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Pédiatrie Enfants - Hématologie Oncologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service des Maladies Infectieuses, CHU Grenoble, Service de Pédiatrie Médicale [Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hémato-oncologie Pédiatrique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Trousseau [APHP], Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Département d'Oncologie Pédiatrique [CHU Hautepierre, Strasbourg], Hôpital de Hautepierre [Strasbourg], Immunologie clinique [CHU St-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine de l'enfant et de l'adolescent [CHU Rennes], Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours (UT), Ecole Polytechnique Fédérale de Lausanne (EPFL), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Service d'informatique médicale et biostatistiques [CHU Necker], Université de Reims Champagne-Ardenne (URCA), Institut d’Hémato-Oncologie Pédiatrique, Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), service de Médecine Interne et d'Immunologie Clinique [AP-HP Hôpital Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris (AP-HP), Internal Medicine, Paris, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Catalysis, Synthesis of Biomolecules and Sustainable Development (CSB2D), Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Biostatistique et de Recherche Clinique (UBRC), Dept of Physiology, McGill University = Université McGill [Montréal, Canada], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut Jean Godinot [Reims], UNICANCER, Service d'Immunopathologie Clinique, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service Immuno Hémato-Onco Pédiatrique, Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service Hématologie Infantile, Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département de Médecine Interne, Immunologie clinique et maladies infectieuses [CHU Reims], Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie et d'Oncologie pédiatrique, Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Service de pneumologie pédiatrique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Protéines de défense des réponses immune et inflammatoire : identification, régulation et rôles physiopathologiques, Médecine Interne, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Pediatrie Debrousse, Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Combustion, Aérothermique, Réactivité et Environnement (ICARE), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Institut des Sciences de l'Ingénierie et des Systèmes (INSIS - CNRS), Service d'Hématologie et d'Oncologie Médicale, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service d'hémato-immuno-oncologie pédiatrique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Etablissement français du sang [Poitiers] (EFS), Public Health Department, Hôpital de l'Archet, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Innate immunity and Immunotherapy (CRCINA - Département INCIT - Equipe 7), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de médecine interne, Hôpital Universitaire d'Amiens, CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Service de médecine interne, hôpital Purpan, Hôpital Sud, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Service d’oncologie hématologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine de l'enfant et de l'adolescent, CHU Pontchaillou [Rennes]-Hôpital Sud, Apoptose et Progression tumorale (CRCNA / Equipe 9), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Lille Inflammation Research International Center (LIRIC), Université de Tours, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), CHU Toulouse [Toulouse]-Hôpital de Rangueil, Institute of Chemistry for Life and Health Sciences (i-CLEHS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), McGill University, Institut Jean Godinot, CRLCC Jean Godinot, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hématologie pédiatrique, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA), Unité d'Hémato-Oncologie, Hôpital des Enfants, CHU Saint-Etienne, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Institut des Sciences de l'Ingénierie et des Systèmes (INSIS), CHU Saint-Antoine [APHP], École pratique des hautes études (EPHE), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Chaire Médecine expérimentale (A. Fischer), Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Pontchaillou [Rennes]-hôpital Sud, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: Oncology, medicine.medical_specialty, Palliative care, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hematopoietic stem cell transplantation, Donor lymphocyte infusion, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Transplantation, Homologous, Treatment Failure, Child, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, Acute leukemia, Chemotherapy, Leukemia, business.industry, Palliative Care, Hematopoietic Stem Cell Transplantation, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Donor Lymphocytes, Leukemia, Biphenotypic, Acute, 3. Good health, Surgery, Survival Rate, Leukemia, Myeloid, Acute, Treatment Outcome, Lymphocyte Transfusion, 030220 oncology & carcinogenesis, Acute Disease, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, 030215 immunology
Abstract: Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in the case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent 10-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted of chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and donor lymphocyte infusion (DLI; n=30), or isolated reinfusion of donor lymphocytes (DLI; n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy=385 days, second allograft=391 days, chemotherapy=174 days, DLI alone=140 days, palliative care=43 days. A second SCT or a combination of chemotherapy and DLI yielded similar outcome (hazard ratio (HR)=0.85, P=0.53) unlike chemotherapy alone (HR=1.43 P=0.04), palliative care (HR=4.24, P
Published: 2017
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24. Elaboration of a semi-automated algorithm for brain arteriovenous malformation segmentation: initial results

Author: Laffargue, Fanny, Bourthoumieu, Sylvie, Llanas, Brigitte, Baudouin, Véronique, Lahoche, Annie, Morin, Denis, Bessenay, Lucie, De Parscau, Loïc, Cloarec, Sylvie, Delrue, Marie-Ange, Taupiac, Emmanuelle, Dizier, Emilie, Laroche, Cécile, Bahans, Claire, Lacombe, Didier, Guigonis, Vincent, Clarençon, Frédéric, Maizeroi-Eugène, Franck, Bresson, Damien, Maingreaud, Flavien, Sourour, Nader, Couquet, Claude, Ayoub, David, Chiras, Jacques, Yardin, Catherine, Mounayer, Charbel, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre de recherche de l'hôpital Sainte Justine, CHU Sainte Justine [Montréal], Centre de Référence du Sud Ouest des Maladies Rénales Rares, CHU Toulouse [Toulouse]-Hôpital des Enfants, CHU Toulouse [Toulouse], Service de Néphrologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Métal, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie - Hémodialyses [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHRU de Brest - Département de Pédiatrie (CHU BREST Pédiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, Service de Génétique Médicale du CHU de Bordeaux, Service de Pédiatrie médicale [CHU Limoges], CHU Limoges, Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Equipe de Recherche Médicale Appliquée (ERMA), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pharmacologie, Service d'Histologie, cytologie, cytogénétique, biologie cellulaire [CHU Limoges], Service de Neurologie [CHU Limoges], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Intracranial Arteriovenous Malformations, Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Arteriovenous Malformations, Young Adult, Imaging, Three-Dimensional, medicine, Humans, Radiology, Nuclear Medicine and imaging, Segmentation, Complication rate, Child, ComputingMilieux_MISCELLANEOUS, Aged, Neuroradiology, medicine.diagnostic_test, business.industry, Angiography, Digital Subtraction, Reproducibility of Results, Arteriovenous malformation, Venous drainage, General Medicine, Digital subtraction angiography, Middle Aged, medicine.disease, Cerebral Angiography, 3d rotational angiography, Automated algorithm, Female, Radiology, business, Algorithms
Abstract: The purpose of our study was to distinguish the different components of a brain arteriovenous malformation (bAVM) on 3D rotational angiography (3D-RA) using a semi-automated segmentation algorithm. Data from 3D-RA of 15 patients (8 males, 7 females; 14 supratentorial bAVMs, 1 infratentorial) were used to test the algorithm. Segmentation was performed in two steps: (1) nidus segmentation from propagation (vertical then horizontal) of tagging on the reference slice (i.e., the slice on which the nidus had the biggest surface); (2) contiguity propagation (based on density and variance) from tagging of arteries and veins distant from the nidus. Segmentation quality was evaluated by comparison with six frame/s DSA by two independent reviewers. Analysis of supraselective microcatheterisation was performed to dispel discrepancy. Mean duration for bAVM segmentation was 64 ± 26 min. Quality of segmentation was evaluated as good or fair in 93 % of cases. Segmentation had better results than six frame/s DSA for the depiction of a focal ectasia on the main draining vein and for the evaluation of the venous drainage pattern. This segmentation algorithm is a promising tool that may help improve the understanding of bAVM angio-architecture, especially the venous drainage. • The segmentation algorithm allows for the distinction of the AVM’s components • This algorithm helps to see the venous drainage of bAVMs more precisely • This algorithm may help to reduce the treatment-related complication rate
Published: 2014
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25. Activation-induced deaminase in B lymphocyte maturation and beyond

Author: Michel Cogné, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)
Subjects: APOBEC, Activation-induced deaminase, APOBEC-1 Deaminase, Somatic hypermutation, Biology, DNA Mismatch Repair, 03 medical and health sciences, class-switching, 0302 clinical medicine, lymphomagenesis, Cytidine Deaminase, medicine, Activation-induced (cytidine) deaminase, Animals, Humans, lcsh:QH301-705.5, B cell, 030304 developmental biology, 0303 health sciences, B-Lymphocytes, lcsh:R5-920, hypermutation, Germinal center, Cell Differentiation, General Medicine, Germinal Center, Molecular biology, Immunoglobulin Class Switching, medicine.anatomical_structure, Immunoglobulin class switching, lcsh:Biology (General), biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, locus suicide, DNA mismatch repair, lcsh:Medicine (General), 030215 immunology
Abstract: International audience; Activation-induced deaminase (AID), a member of the AID/apolipoprotein B mRNA-editing enzyme-catalytic (APOBEC) family, deaminates DNA cytidines into uridines and is the major trans-acting player of immunoglobulin (Ig) genes' diversification in mature B lymphocytes. It allows multiple antigen-driven Ig modifications through gene conversion and/or somatic hypermutation of variable region genes and also permits to switch from IgM expression to other antibody classes after class switch recombination, or to stop Ig expression after locus suicide recombination. AID is expressed at high levels into germinal center activated B cells with a very stringent temporal and spatial regulation. Despite multiple levels of regulation, off-target effects of AID are quite frequent in the B cell lineage and can affect a number of non-Ig genes, albeit at lower level than Ig genes. Beyond the immune system, AID also contributes to cytosine demethylation in undifferentiated cells by deaminating methylcytosines into thymines which are further processed by thymidine glycosylase. This contributes to the maintenance of pluripotency and to the limitation of genetic imprinting. Since AID attacks on DNA can induce replication errors, base excision repair, or mismatch repair, they are strongly mutagenic and are also driving forces of tumorigenesis, not only in B cell malignancies but also in some non-lymphoid tumors involving ectopic AID expression.
Published: 2013
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26. Baseline differential blood count and prognosis in CD20-positive post-transplant lymphoproliferative disorder in the prospective PTLD-1 trial

Author: F. Morschhauser, Véronique Leblond, Petra Reinke, Ulrich Dührsen, Thierry Lamy, Heiner Zimmermann, Hanno Riess, John Moore, Arnaud Jaccard, Sylvain Choquet, Ralf Ulrich Trappe, Hans B. Lehmkuhl, Malte Leithäuser, Yvon Lebranchu, Gilles Salles, Corrado Tarella, Ruth Neuhaus, Heinz-August Horst, P. Schlattmann, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], and CHU Limoges
Subjects: Cancer Research, Medizin, MESH: Antigens, CD20, Organ transplantation, Postoperative Complications, MESH: Lymphoproliferative Disorders, 0302 clinical medicine, MESH: Postoperative Complications, hemic and lymphatic diseases, Prospective Studies, MESH: Blood Cell Count, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, CD20, biology, MESH: Follow-Up Studies, Hematology, Prognosis, 3. Good health, Survival Rate, surgical procedures, operative, Oncology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.medical_specialty, MESH: Survival Rate, Lymphoproliferative disorders, MESH: Organ Transplantation, Differential blood count, MESH: Prognosis, Post-transplant lymphoproliferative disorder, 03 medical and health sciences, Internal medicine, mental disorders, medicine, Humans, Survival rate, Retrospective Studies, MESH: Humans, business.industry, MESH: Retrospective Studies, Retrospective cohort study, Organ Transplantation, Antigens, CD20, medicine.disease, Lymphoproliferative Disorders, MESH: Prospective Studies, Blood Cell Count, Surgery, biology.protein, business, Follow-Up Studies, 030215 immunology
Abstract: Baseline differential blood count and prognosis in CD20-positive post-transplant lymphoproliferative disorder in the prospective PTLD-1 trial
Published: 2013
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27. Prognostic value of left atrial function in systemic light-chain amyloidosis: a cardiac magnetic resonance study

Author: Frank Bridoux, Dania Mohty, Bahaa M. Fadel, Sylvain Martin, Nicolas Varroud-Vial, Arnaud Jaccard, Cyrille Boulogne, Victor Aboyans, Julien Magne, Thibaud Damy, Hind Ettaif, Service de cardiologie [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Service de Néphrologie CHU Poitiers, Unité fonctionnelle insuffisance cardiaque, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est (UPE), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Cardio-vascular diseases, and Clinical sciences
Subjects: Male, Databases, Factual, Cardiac magnetic resonance, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Severity of Illness Index, 030218 nuclear medicine & medical imaging, Cohort Studies, 0302 clinical medicine, Left atrial, Medicine, Immunoglobulin Light-chain Amyloidosis, Prospective Studies, Ejection fraction, Amyloidosis, Age Factors, General Medicine, Middle Aged, Prognosis, 3. Good health, Cardiology, Female, France, AL amyloidosis, Cardiomyopathies, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Diastole, Magnetic Resonance Imaging, Cine, Immunoglobulin light chain, Risk Assessment, 03 medical and health sciences, Sex Factors, Predictive Value of Tests, Internal medicine, Image Interpretation, Computer-Assisted, Confidence Intervals, Humans, Radiology, Nuclear Medicine and imaging, Heart Atria, Left atrial function, Aged, Proportional Hazards Models, Analysis of Variance, business.industry, Stroke Volume, medicine.disease, Survival Analysis, ROC Curve, Cardiac amyloidosis, Immunoglobulin Light Chains, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background Cardiac involvement in systemic light-chain amyloidosis (AL) imparts an adverse impact on outcome. The left atrium (LA), by virtue of its anatomical location and muscular wall, is commonly affected by the amyloid process. Although LA infiltration by amyloid fibrils leads to a reduction in its pump function, the infiltration of the left ventricular (LV) myocardium results in diastolic dysfunction with subsequent increase in filling pressures and LA enlargement. Even though left atrial volume (LAV) is an independent prognostic marker in many cardiomyopathies, its value in amyloid heart disease remains to be determined. In addition, few data are available as to the prognostic value of LA function in systemic AL. Using cardiac magnetic resonance (CMR), the current study aims to assess the prognostic significance of the maximal LAV and total LA emptying fraction (LAEF) in patients with AL. Methods and results Fifty-four consecutive patients (age 66 +/- 10 years, 59% males) with confirmed systemic AL and mean LV ejection fraction of 60 +/- 12% underwent CMR. As compared with patients with no or minimal cardiac involvement (Mayo Clinic [MC] stage I), those at moderate and high risk (MC stages II and III) had significantly larger indexed maximal LAV (36 +/- 15 vs. 46 +/- 13 vs. 52 +/- 19 mL/m(2), P = 0.03) and indexed minimal LAV (20 +/- 6 vs. 34 +/- 11 vs. 44 +/- 17 mL/m2, P < 0.001), lower LAEF (42 +/- 9 vs. 26 +/- 13 vs. 16 +/- 9%, P < 0.0001) but similar LVEF. Furthermore, myocardial late gadolinium enhancement (LGE) was more frequent and significantly associated with lower LAEF. LAEF was also significantly lower in symptomatic (NHYA >= II, 22 +/- 14%) as compared with asymptomatic patients (NYHA class I, 33 +/- 13%, P = 0.006). Two-year survival rate was lower in patients with LAEF 16% (37 +/- 11 vs. 94 +/- 4%, P = 0.001). In multivariate analysis, lower LAEF remained independently associated with a higher risk of 2-year mortality (HR = 1.08 per 1% decrease, 95%CI: 1.02-1.15, P = 0.003). Conclusion In patients with systemic AL, LAEF as assessed by CMR is associated with NYHA functional class, MC stage, myocardial LGE and 2-year mortality.
Published: 2016
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28. Topical Sodium Thiosulfate: A Treatment for Calcifications in Hyperphosphatemic Familial Tumoral Calcinosis?

Author: Karelle Benistan, Hadile Mutar, Elodie Pfender, Agnès Linglart, Claire Bahans, Marie Courbebaisse, Voa Ratsimbazafy, Jeremy Jost, Tu-Anh Tran, Anne Lienhardt, Vincent Guigonis, Agrosystèmes Cultivés et Herbagers (ARCHE), Institut National de la Recherche Agronomique (INRA)-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'endocrinologie pédiatrique [CHU Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service de Pharmacie Centrale [CHU Limoges], Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure Agronomique de Toulouse-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL)
Subjects: Adult, Male, medicine.medical_specialty, Hyperostosis, Administration, Topical, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Thiosulfates, 030209 endocrinology & metabolism, Context (language use), Sodium thiosulfate, Biochemistry, 03 medical and health sciences, Hyperphosphatemia, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Humans, Child, Adverse effect, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, Biochemistry (medical), Calcinosis, Metabolic acidosis, Retrospective cohort study, Prognosis, medicine.disease, Hyperostosis, Cortical, Congenital, 3. Good health, Treatment Outcome, chemistry, Systemic administration, Female, business
Abstract: Hyperphosphatemic familial tumoral calcinosis (HFTC) and hyperphosphatemia hyperostosis syndrome (HHS) are rare diseases characterized by hyperphosphatemia and ectopic calcifications or recurrent episodes of diaphysitis. In the setting of metabolic or inflammatory diseases, recent data suggest that systemic administration of sodium thiosulfate (STS) could be effective in the treatment of ectopic calcifications but may also be poorly tolerated (digestive symptoms, metabolic acidosis). Our group developed a topical formulation of STS to treat ectopic calcifications locally, therefore limiting patient exposure to the drug and its adverse effects.We aimed at describing efficacy and tolerance for a topical formulation of STS in treated patients.We performed a retrospective study wherein clinical, radiological, and biological data before and after the application of the topical STS treatment were collected and analyzed.Three patients admitted to 3 different hospitals with an ectopic calcification secondary to HFTC or HHS were treated with topical STS.The topical STS was applied daily by the patients.A significant clinical and radiological decrease of ectopic calcifications was observed after at least 5 months of treatment. The STS treatment was well tolerated and no clinical or biological side effects were observed.Topical STS appears to be a promising treatment for ectopic calcifications secondary to HFTC or HHS.
Published: 2016
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29. Maladie de dépôts d’immunoglobulines monoclonales de type Randall : du diagnostic au traitement

Author: Frank Bridoux, Jean-Paul Fermand, Bertrand Knebelmann, Arnaud Jaccard, Bertrand Arnulf, Vincent Javaugue, Christophe Sirac, Camille Cohen, Florent Joly, Guy Touchard, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Département de Néphrologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Néphrologie CHU Poitiers, Département de Néphrologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), and CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: medicine.medical_specialty, Bortezomib, business.industry, 030232 urology & nephrology, Plasma cell, medicine.disease, Immunoglobulin light chain, Gastroenterology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Autologous stem-cell transplantation, Nephrology, 030220 oncology & carcinogenesis, Internal medicine, Monoclonal, medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Complication, ComputingMilieux_MISCELLANEOUS, medicine.drug, Kidney disease, Monoclonal Immunoglobulin Deposition Disease
Abstract: Monoclonal immunoglobulin (Ig) deposition disease (MIDD) is a rare complication of plasma cell disorders, defined by linear Congo red-negative deposits of monoclonal light chain (LCDD), heavy chain (HCDD) or both (LHCDD) along basement membranes. MIDD should be suspected in patients presenting with glomerular proteinuria and monoclonal gammopathy, but none of these criteria is necessary for the diagnosis although renal involvement is prominent. Since an abnormal serum κ/λ ratio is found in virtually all MIDD patients, including those with HCDD, serum free light chain assay should be included in the initial workup in patients older than 50 presenting with kidney disease. Bortezomib-based regimens are efficient and well tolerated, resulting in improvement in both renal and global survival, comparatively to historical series. High dose melphalan with autologous stem cell transplantation may be proposed as second line therapy in selected patients. The achievement of hematological response, based on the difference between involved and uninvolved serum free light chains (dFLC), is mandatory. In a recent series, post-treatment dFLC
Published: 2016
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30. Enhancers Located in Heavy Chain Regulatory Region (hs3a, hs1,2, hs3b, and hs4) Are Dispensable for Diversity of VDJ Recombination

Author: Michel Cogné, Yves Denizot, Christelle Vincent-Fabert, Pauline Rouaud, Eric Pinaud, Rémi Fiancette, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Université de Limoges (UNILIM)
Subjects: MESH: V(D)J Recombination, MESH: Mice, Mutant Strains, Cellular differentiation, Immunology, chemical and pharmacologic phenomena, Locus (genetics), Biology, MESH: Genetic Loci, Biochemistry, Genome, Mice, 03 medical and health sciences, 0302 clinical medicine, Intergenic region, MESH: B-Lymphocytes, Animals, MESH: Animals, Enhancer, MESH: Mice, Molecular Biology, 030304 developmental biology, Genetics, B-Lymphocytes, 0303 health sciences, V(D)J recombination, Cell Biology, Molecular biology, Mice, Mutant Strains, V(D)J Recombination, Enhancer Elements, Genetic, Genetic Loci, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin heavy chain, MESH: Enhancer Elements, Genetic, Immunoglobulin Heavy Chains, Recombination, MESH: Immunoglobulin Heavy Chains, 030215 immunology
Abstract: International audience; V(D)J recombination occurs during the antigen-independent early steps of B-cell ontogeny. Multiple IgH cis-regulatory elements control B-cell ontogeny. IGCR1 (intergenic control region 1), the DQ52 promoter/enhancer, and the intronic Emu enhancer, all three located upstream of Cmu, have important roles during V(D)J recombination, whereas there is no clue about a role of the IgH regulatory region (RR) encompassing the four transcriptional enhancers hs3a, hs1,2, hs3b, and hs4 during these early stages. To clarify the role of the RR in V(D)J recombination, we totally deleted it in the mouse genome. Here, we show that V(D)J recombination is unaffected by the complete absence of the IgH RR, highlighting that this region only orchestrates IgH locus activity during the late stages of B-cell differentiation. In contrast, the earliest antigen-independent steps of B-cell ontogeny would be under the control of only the upstream Cmu elements of the locus.
Published: 2012
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31. A p53 Defect Sensitizes Various Stages of B Cell Development to Lymphomagenesis in Mice Carrying an IgH 3′ Regulatory Region-Driven c-myc Transgene

Author: Michel Cogné, Virginie Magnone, Brice Laffleur, Yves Denizot, Pauline Rouaud, Rémi Fiancette, Christelle Vincent-Fabert, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiological Genomics of the Eukaryotes, and Université de Limoges (UNILIM)
Subjects: Lymphoma, Genes, myc, MESH: Flow Cytometry, Cell Separation, Regulatory Sequences, Nucleic Acid, Plasma cell, Mice, 0302 clinical medicine, immune system diseases, MESH: Reverse Transcriptase Polymerase Chain Reaction, hemic and lymphatic diseases, Plasma cell differentiation, Immunology and Allergy, MESH: Animals, Transgenes, MESH: Tumor Suppressor Protein p53, Oligonucleotide Array Sequence Analysis, B-Lymphocytes, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, MESH: Enzyme-Linked Immunosorbent Assay, Flow Cytometry, 3. Good health, Cell Transformation, Neoplastic, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin Heavy Chains, MESH: Immunoglobulin Heavy Chains, MESH: Mice, Transgenic, Immunology, MESH: Transgenes, Enzyme-Linked Immunosorbent Assay, Mice, Transgenic, Biology, MESH: Cell Separation, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: B-Lymphocytes, medicine, MESH: Regulatory Sequences, Nucleic Acid, Animals, MESH: Mice, MESH: Genes, myc, B cell, 030304 developmental biology, CD43, Oncogene, medicine.disease, Virology, Mice, Inbred C57BL, Immunoglobulin class switching, MESH: Cell Transformation, Neoplastic, MESH: Oligonucleotide Array Sequence Analysis, Cancer research, Mantle cell lymphoma, Tumor Suppressor Protein p53, MESH: Lymphoma
Abstract: Although c-myc is classically described as the driving oncogene in Burkitt’s lymphoma (BL), deregulation and mutations of c-myc have been reported in multiple solid tumors and in other mature B cell malignancies such as mantle cell lymphoma (MCL), myeloma, and plasma cell lymphoma (PCL). After translocation into the IgH locus, c-myc is constitutively expressed under the control of active IgH enhancers. Those located in the IgH 3′ regulatory region (3′RR) are master control elements of class switch recombination and of the transcriptional burst associated with plasma cell differentiation. c-myc-3′RR mice are prone to lymphomas with rather homogeneous, most often BL-like, phenotypes with incomplete penetrance (75% tumor incidence) and long latencies (10–12 mo). To reproduce c-myc–induced mature B cell lymphomagenesis in the context of an additional defect often observed in human lymphomas, we intercrossed c-myc-3′RR with p53+/− mice. Double transgenic c-myc-3′RR/p53+/− mice developed lymphoma with short latency (2–4 mo) and full penetrance (100% tumor incidence). The spectrum of B lymphomas occurring in c-myc-3′RR/p53+/− mice was widened, including nonactivated (CD43−) BL, activated (CD43+) BL, MCL-like lymphoma, and PCL, thus showing that 3′RR-mediated deregulation of c-myc can promote various types of B lymphoproliferation in cells that first acquired a p53 defect. c-myc/p53+/− mice closely reproduce many features of BL, MCL, and PCL and provide a novel and efficient model to dissect the molecular events leading to c-myc–induced lymphomagenesis and an important tool to test potential therapeutic agents on malignant B cells featuring various maturation stages.
Published: 2011
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32. Non-invasive detection of hepatic amyloidosis: FibroScan, a new tool

Author: Anne-Laure Fauchais, Dominique Bordessoule, Paul Carrier, Annie Lefebvre, Arnaud Jaccard, Julie Abraham, Fatima Yagoubi, Anne Cypierre, Véronique Loustaud-Ratti, Annick Rousseau, Elisabeth Vidal, Denis Sautereau, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'Hématologie biologique [CHU Limoges], Université de Limoges (UNILIM), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pathology, medicine.medical_specialty, Heart disease, Hepatitis C virus, Hepatic amyloidosis, Plaque, Amyloid, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, medicine, AL amyloidosis, Humans, In patient, 030304 developmental biology, 0303 health sciences, business.industry, Liver Diseases, Non invasive, Amyloidosis, Hepatitis C, Hepatitis C, Chronic, medicine.disease, Elasticity, 3. Good health, Amyloid deposition, Liver, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Elasticity Imaging Techniques, business
Abstract: International audience; Introduction. FibroScan, a non-invasive tool for measuring liver stiffness (LS), is not specific to liver fibrosis. Other extra-hepatic conditions may modify the LS value. Objectives. Our aim was to examine whether amyloid deposition in the liver may modify LS. Methods. LS was measured prospectively in 41 patients with systemic AL amyloidosis (AL) in the French AL Reference Center, comprising: 5 patients with liver involvement (LI) and no cardiac involvement (CI), 11 with CI and no LI, 12 with both LI and CI and 13 with neither (2005 consensus criteria); 26 negative controls, 50 patients infected with Hepatitis C virus (HCV)-infected and 18 AL-free patients with right-sided heart disease ('cardiac controls') were also examined. Results. Median LS was significantly higher in patients with AL with liver involvement [27.4 (10.3-75) kPa] than in negative controls [4.8 (2.8-11.9) kPa] (p 17.3 kPa is suggestive of AL hepatic disease in patients with non-fibrotic liver changes, and may have diagnostic value in patients with known AL.
Published: 2011
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33. The IgH 3′ regulatory region and its implication in lymphomagenesis

Author: Michel Cogné, Yves Denizot, Christelle Vincent-Fabert, Rémi Fiancette, Eric Pinaud, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Université de Limoges (UNILIM)
Subjects: Lymphoma, Transgene, Immunology, Mice, Transgenic, Chromosomal translocation, Lymphocyte proliferation, Regulatory Sequences, Nucleic Acid, Biology, Regulatory region, Mice, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), Animals, Humans, Immunology and Allergy, 3' Untranslated Regions, Gene, 030304 developmental biology, Genetics, B-Lymphocytes, 0303 health sciences, Disease Models, Animal, Cell Transformation, Neoplastic, Immunoglobulin class switching, Regulatory sequence, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin Heavy Chains
Abstract: International audience; The 3' regulatory region (3'RR) located downstream of the IgH gene is the master element that controls class switch recombination and sustains high-level transcription at the plasma-cell stage. This latter role suggests that the 3'RR may be involved in oncogene deregulation during the frequent IgH translocation events associated with B-cell malignancies. A convincing demonstration of the essential contribution of 3'RR in lymphomagenesis has been provided by transgenic animal models. The mouse 3'RR shares a strong structural homology with the regulatory regions located downstream of each human Cα gene. Mouse models exploring the role of the 3'RR in B-cell physiology and in malignancies should provide useful indications about the pathophysiology of human cell lymphocyte proliferation.
Published: 2010
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34. Involvement of Human Herpesvirus-6 Variant B in Classic Hodgkin's Lymphoma via DR7 Oncoprotein

Author: Dominique Bordessoule, Pierre-Marie Preux, Sophie Collot-Teixeira, Aurélie Lacroix, Sylvie Ranger-Rogez, Christophe Piguet, Laurent Mardivirin, Arnaud Jaccard, Barbara Petit, Franck Sturtz, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale et Comparée (NETEC), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges (UNILIM), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), Laboratoire de Biostatistique et d'Informatique Médicale, Université de Limoges (UNILIM), and Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges]
Subjects: Adult, Male, Cancer Research, Multiple Sclerosis, Adolescent, Herpesvirus 6, Human, viruses, education, Biology, Young Adult, 03 medical and health sciences, Transactivation, 0302 clinical medicine, Nodular sclerosis, Western blot, medicine, Humans, health care economics and organizations, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Reporter gene, medicine.diagnostic_test, virus diseases, Oncogenes, Middle Aged, medicine.disease, Hodgkin's lymphoma, biology.organism_classification, Hodgkin Disease, Virology, Molecular biology, 3. Good health, Lymphoma, Oncology, Cell culture, 030220 oncology & carcinogenesis, Trans-Activators, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Human herpesvirus 6
Abstract: Purpose: Hodgkin's lymphoma (HL) is associated with the presence of EBV in Reed-Sternberg (RS) cells in ∼40% of cases. Here, we studied the presence of human herpesvirus type 6 (HHV-6) variant B in RS cells of HL patients and correlated results with clinical parameters. We then examined the implication of HHV-6 DR7B protein in cell deregulation. Experimental Design: HHV-6 DR7B protein was produced in a Semliki Forest virus system. Polyclonal antibodies were then generated and used for immunochemical HHV-6 localization in HL biopsies. Binding between DR7B and p53 was studied using a double-hybrid system. Transactivation of NFκB was observed after transient transfection using reporter gene assays. We looked for Id2 factor expression after stable transfection of the BJAB cell line by reverse transcription-PCR and Western blot analysis. Results: HHV-6 was more common in nodular sclerosis subtype HL, and DR7B oncoprotein was detected in RS cells for 73.7% of EBV-negative patients. Colocalization of EBV and HHV-6 was observed in RS cells of doubly infected patients. DR7B protein bound to human p53 protein. p105-p50/p65 mRNA expression and activation of the NFκB complex were increased when DR7B was expressed. Stable expression of DR7B exhibited a strong and uniform expression of Id2. A slightly higher percentage of remission was observed in patients with RS cells testing positive for DR7B than in those testing negative. Conclusions: Collectively, these data provide evidence for the implication of a novel agent, HHV-6, in cases of nodular sclerosis HL. Clin Cancer Res; 16(19); 4711–21. ©2010 AACR.
Published: 2010
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35. Genomic deletion of the whole IgH 3′ regulatory region (hs3a, hs1,2, hs3b, and hs4) dramatically affects class switch recombination and Ig secretion to all isotypes

Author: Véronique Truffinet, Michel Cogné, Yves Denizot, Rémi Fiancette, Nadine Cogné, Christelle Vincent-Fabert, Eric Pinaud, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Université de Limoges (UNILIM)
Subjects: Transcription, Genetic, Immunology, chemical and pharmacologic phenomena, Apoptosis, Enzyme-Linked Immunosorbent Assay, Mice, Inbred Strains, Regulatory Sequences, Nucleic Acid, Plasma cell, Biochemistry, Immunoglobulin D, Cell Line, Mice, 03 medical and health sciences, 0302 clinical medicine, Plasma cell differentiation, medicine, Animals, Enhancer, Cells, Cultured, Cell Proliferation, Sequence Deletion, 030304 developmental biology, Mice, Knockout, Recombination, Genetic, B-Lymphocytes, 0303 health sciences, biology, Reverse Transcriptase Polymerase Chain Reaction, Cell Biology, Hematology, Flow Cytometry, Immunoglobulin Class Switching, Isotype, Molecular biology, Immunoglobulin Isotypes, medicine.anatomical_structure, Immunoglobulin M, Immunoglobulin class switching, Regulatory sequence, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin heavy chain, Immunoglobulin Heavy Chains, 030215 immunology
Abstract: The immunoglobulin heavy chain locus (IgH) undergoes multiple changes along B-cell differentiation. In progenitor B cells, V(D)J assembly allows expression of μ heavy chains. In mature B cells, class switch recombination may replace the expressed constant (C)μ gene with a downstream CH gene. Finally, plasma cell differentiation strongly boosts IgH transcription. How the multiple IgH transcriptional enhancers tune these changes is unclear. Here we demonstrate that deletion of the whole IgH 3′ regulatory region (3′RR) allows normal maturation until the stage of IgM/IgD expressing lymphocytes, but nearly abrogates class switch recombination to all CH genes. Although plasma cell numbers are unaffected, we reveal the role of the 3′RR into the transcriptional burst normally associated with plasma cell differentiation. Our study shows that transcriptional changes and recombinations occurring after antigen-encounter appear mainly controlled by the 3′RR working as a single functional unit.
Published: 2010
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36. A myeloma translocation-like model associating CCND1 with the immunoglobulin heavy-chain locus 3′ enhancers does not promote by itself B-cell malignancies

Author: Michel Cogné, Yves Denizot, Rémi Fiancette, Christelle Vincent-Fabert, Rada Amin, Nadine Cogné, Véronique Truffinet, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Université de Limoges (UNILIM)
Subjects: Male, MESH: Cyclin D1, Cancer Research, MESH: Spleen, MESH: Flow Cytometry, Apoptosis, Proto-Oncogene Mas, Immunoenzyme Techniques, Mice, 0302 clinical medicine, MESH: Genetic Vectors, Bone Marrow, MESH: Reverse Transcriptase Polymerase Chain Reaction, hemic and lymphatic diseases, MESH: Animals, Cyclin D1, Multiple myeloma, B-Lymphocytes, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Cell Differentiation, Hematology, Cell cycle, Flow Cytometry, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Bone Marrow, Immunoglobulin Heavy Chains, MESH: Immunoglobulin Heavy Chains, MESH: Cell Differentiation, MESH: Mice, Transgenic, Transgene, Blotting, Western, Genetic Vectors, Mice, Transgenic, Biology, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: B-Lymphocytes, MESH: Cell Proliferation, medicine, MESH: Blotting, Western, Animals, RNA, Messenger, MESH: Immunoenzyme Techniques, MESH: Mice, B cell, Locus control region, MESH: RNA, Messenger, Cell Proliferation, 030304 developmental biology, MESH: Apoptosis, medicine.disease, MESH: Male, Mice, Inbred C57BL, Disease Models, Animal, Immunoglobulin class switching, Cancer research, Mantle cell lymphoma, MESH: Disease Models, Animal, Spleen
Abstract: International audience; Cyclin D1 overexpression is associated with mantle cell lymphoma and multiple myeloma. In myeloma, it often results from chromosomal translocations linking the CCND1 gene to the 3' part of the IgH locus constant region. This region includes a single and potent transcriptional regulatory region (RR) 3' of the Calpha gene mostly active in mature B-cells. To check whether this RR alone was sufficient to deregulate CCND1, we generated mice carrying a 3'IgH RR-driven human CCND1 transgene and specifically up-regulating cyclin D1 expression in B-cells. In transgenic B-cells, cyclin D1 enforced cell cycle entry in response to various stimuli (LPS, anti-IgM, anti-CD40) but also increased cell death, so that exaggerated proliferation did not result in peripheral lymphocytosis. Despite exaggerated B-cell entry into G(1) phase, malignant lymphoproliferation did not occur either. Crossing of CCND1-3'IgH RR mice with c-myc-3'IgH RR mice did not reveal accelerated tumorigenesis as compared with c-myc-3'IgH RR mice alone. The data presented here demonstrate that the 3'IgH RR-mediated deregulation of CCND1 in mature B-cells cannot by itself trigger the development of lymphomas and strengthen the concept that cyclin D1 per se is not an armful proto-oncogene. Rather its overexpression in several malignancies might be only a stigma of lymphomagenesis or represent a single hit within a multiple hit process.
Published: 2010
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37. Inkjet-Printing-Engineered Functional Microdot Arrays Made of Mesoporous Hybrid Organosilicas

Author: Clément Sanchez, Martine Lejeune, Claire Carrion, Bernard Soulestin, Cédric Boissière, B. Fousseret, Fabrice Rossignol, François Ribot, M. Mougenot, Dominique Jalabert, Jean-François Baumard, Science des Procédés Céramiques et de Traitements de Surface (SPCTS), Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Axe 1 : procédés céramiques, Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut des Procédés Appliqués aux Matériaux (IPAM), Laboratoire de Chimie de la Matière Condensée de Paris (site Paris VI) (LCMCP (site Paris VI)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Microscopie Electronique, Université d'Orléans (UO), Centre universitaire de Cytométrie, Imagerie et Mathématiques (CIM), Université de Limoges (UNILIM)-CHU Limoges, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and European Project
Subjects: Materials science, Fabrication, General Chemical Engineering, Microdot, Nanotechnology, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, Colloid, Membrane, Materials Chemistry, 0210 nano-technology, Mesoporous material, Hybrid material, Porosity, Inkjet printing
Abstract: International audience; The fabrication of three-dimensional fine-scale microdot arrays of organized mesoporous hybrid organosilicas by the coupling of inkjet printing (IJP) and Pluronic F127 driven evaporation-induced self-assembly (EISA) in the presence of cocondensed silica and organosilica precursors is demonstrated. The mesoorganization can be optimized by tuning both processing and chemical parameters (the drying time between successive layers, droplet volume, chemical composition, temperature, and aging time of the colloidal sol). The feasibility of one-pot multifunctionalization with both TFTS CF3(CF2)5CH2CH2Si(OC2H5)3 and thiol functionalities HSCH2CH2CH2Si(OC2H5)3 is also demonstrated, emphasizing the wide range of accessible nanostructured porous hybrid materials that result from the coupling of IJP and EISA. From this demonstrative concept, many hybrid materials with applications in the field of multiarray sensors and smart membranes can be expected. Moreover, the peculiar role of the hydrophobic organosilane TFTS CF3(CF2)5CH2CH2Si(OC2H5)3, as promoter of the structural mesoorganization of hybrid microdots, is discussed. The hydrophobic nature of microdot arrays is characterized as a function of TFTS addition and surface morphology. Tuning both the amount of the hydrophobic component and microdot-induced surface patterning allows controlled one-pot synthesis of hyperhydrophobic surfaces with contact angles rising up to 131. Moreover, the possibility of grafting via one-pot synthesis a thiol function, allowing the trapping of gold nanoparticles, is demonstrated.
Published: 2010
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38. Multiple RNA Surveillance Mechanisms Cooperate to Reduce the Amount of Nonfunctional Igκ Transcripts

Author: Guillaume Chemin, Michel Cogné, Aurélien Tinguely, Fabien Lechouane, Sophie Duchez, Laurent Delpy, Christophe Sirac, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Université de Limoges (UNILIM)
Subjects: Transcription, Genetic, MESH: Gene Rearrangement, B-Lymphocyte, Light Chain, MESH: Codon, Terminator, MESH: Down-Regulation, Mice, 0302 clinical medicine, Transcription (biology), Gene Rearrangement, B-Lymphocyte, Light Chain, Immunology and Allergy, MESH: Animals, MESH: Codon, Nonsense, Frameshift Mutation, Recombination, Genetic, Genetics, MESH: Plasma Cells, 0303 health sciences, Stem Cells, MESH: Frameshift Mutation, Cell Differentiation, medicine.anatomical_structure, Codon, Nonsense, RNA splicing, Codon, Terminator, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Recombination, Genetic, MESH: Cell Differentiation, MESH: Cell Line, Tumor, RNA Splicing, Plasma Cells, Immunology, MESH: Immunoglobulin kappa-Chains, Down-Regulation, MESH: Stem Cells, Biology, Frameshift mutation, Immunoglobulin kappa-Chains, 03 medical and health sciences, Cell Line, Tumor, medicine, Animals, RNA, Messenger, MESH: Mice, Gene, Alleles, B cell, MESH: RNA, Messenger, 030304 developmental biology, Messenger RNA, MESH: Alleles, MESH: Transcription, Genetic, RNA surveillance, Open reading frame, MESH: RNA Splicing, 030215 immunology
Abstract: Random V(D)J junctions ensure that the diversity of the Ig primary repertoire is adapted to the vast heterogeneity of Ags. In two-thirds of cases, recombination between variable segments induces a frameshift in the open reading frame and generates a premature termination codon. In B cells harboring biallelic V(D)J rearrangement of Ig genes, transcription is known to occur on both the functional and nonfunctional alleles, generating considerable amounts of primary transcripts with out-of-frame V regions. In this study, we analyzed in cell lines and primary B cells the RNA surveillance of nonfunctional Igκ transcripts arising from nonproductive rearrangement. We demonstrated that splicing inhibition, nonsense-mediated decay and nonsense-altered splicing each have an individual partial effect that together associate into an efficient surveillance machinery, downregulating nonfunctional Igκ mRNA. Moreover, we provide evidence that the RNA surveillance efficiency increases throughout B cell development. Whereas splicing inhibition remains constant in most cell lines, differences in nonsense-mediated decay and nonsense-altered splicing are responsible for the higher RNA surveillance observed in plasma cells. Altogether, these data show that nonfunctionally rearranged alleles are subjected to active transcription but that multiple RNA surveillance mechanisms eradicate up to 90% of out-of-frame Igκ mRNA.
Published: 2010
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39. Premature replacement of μ with α immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation

Author: Sophie Duchez, Virginie Pascal, Nadine Cogné, Blaise Corthésy, Michel Cogné, Laurent Delpy, Christophe Sirac, Rada Amin, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Université de Limoges (UNILIM)
Subjects: Plasma Cells, B-cell receptor, Receptors, Antigen, B-Cell, Mice, Transgenic, Biology, Plasma cell, Immunoglobulin alpha-Chains, Mice, 03 medical and health sciences, 0302 clinical medicine, Plasma cell differentiation, medicine, Animals, Humans, Lymphopoiesis, B cell, 030304 developmental biology, B-Lymphocytes, 0303 health sciences, Multidisciplinary, Immunoglobulin mu-Chains, Reverse Transcriptase Polymerase Chain Reaction, breakpoint cluster region, Biological Sciences, Flow Cytometry, Immunohistochemistry, Molecular biology, J chain, medicine.anatomical_structure, Bromodeoxyuridine, Gene Targeting, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, 030215 immunology
Abstract: International audience; Sequentially along B cell differentiation, the different classes of membrane Ig heavy chains associate with the Igalpha/Igbeta heterodimer within the B cell receptor (BCR). Whether each Ig class conveys specific signals adapted to the corresponding differentiation stage remains debated. We investigated the impact of the forced expression of an IgA-class receptor throughout murine B cell differentiation by knocking in the human Calpha Ig gene in place of the Smu region. Despite expression of a functional BCR, homozygous mutant mice showed a partial developmental blockade at the pro-B/pre-BI and large pre-BII cell stages, with decreased numbers of small pre-BII cells. Beyond this stage, peripheral B cell compartments of reduced size developed and allowed specific antibody responses, whereas mature cells showed constitutive activation and a strong commitment to plasma cell differentiation. Secreted IgA correctly assembled into polymers, associated with the murine J chain, and was transported into secretions. In heterozygous mutants, cells expressing the IgA allele competed poorly with those expressing IgM from the wild-type allele and were almost undetectable among peripheral B lymphocytes, notably in gut-associated lymphoid tissues. Our data indicate that the IgM BCR is more efficient in driving early B cell education and in mucosal site targeting, whereas the IgA BCR appears particularly suited to promoting activation and differentiation of effector plasma cells.
Published: 2010
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40. Genetic background modulates susceptibility to oncogen-driven proliferation and lymphoma occurrence in mice carrying a deregulated c-myc transgene

Author: Yves Denizot, Rémi Fiancette, Christelle Vincent-Fabert, Nadine Cogné, Michel Cogné, Véronique Truffinet, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Université de Limoges (UNILIM)
Subjects: Male, Cancer Research, Lymphoma, MESH: Mice, Transgenic, Transgene, Genes, myc, MESH: Mice, Inbred BALB C, Mice, Transgenic, MESH: Transgenes, Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, MESH: Mice, Inbred C57BL, MESH: Cell Proliferation, medicine, Animals, Genetic Predisposition to Disease, MESH: Animals, Transgenes, MESH: Mice, ComputingMilieux_MISCELLANEOUS, MESH: Genes, myc, Cell Proliferation, 030304 developmental biology, Mice, Inbred BALB C, 0303 health sciences, Cell growth, MESH: Genetic Predisposition to Disease, Hematology, medicine.disease, Virology, MESH: Male, Mice transgenic, Mice, Inbred C57BL, Oncology, 030220 oncology & carcinogenesis, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Lymphoma, MESH: Female
Abstract: International audience
Published: 2009
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41. Analysis of the Ten-Eleven Translocation 2 (TET2) gene in familial myeloproliferative neoplasms

Author: Yves Plumelle, Albert Najman, Dominique Bordessoule, Isabelle Plo, Sabrina Dupont, William Vainchenker, Olivier Bernard, François Delhommeau, Alain Devidas, Christine Bellanné-Chantelot, Christine Chomienne, Françoise Isnard, Gwendoline Leroy, Chloé James, Cécile Saint-Martin, Martine Gardembas-Pain, André Delannoy, Gérard Panelatti, Hematopoïèse et Cellules Souches (U362), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'Hématologie biologique [CHU Limoges], Université de Limoges (UNILIM), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Granulopoiese et Processus Leucemiques (UMR_S_718), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université René Descartes, Hematopoïese et cellules souches normales et pathologiques (U790), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, DNA Mutational Analysis, medicine.disease_cause, Biochemistry, 0302 clinical medicine, Polycythemia vera, hemic and lymphatic diseases, MESH: DNA Mutational Analysis, Cells, Cultured, MESH: Aged, Genetics, 0303 health sciences, Mutation, MESH: Middle Aged, MESH: Genetic Predisposition to Disease, food and beverages, Myeloid leukemia, Hematology, Middle Aged, Pedigree, 3. Good health, DNA-Binding Proteins, Phenotype, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Myeloproliferative Disorders, MESH: Cells, Cultured, Adult, Tumor suppressor gene, MESH: Pedigree, Immunology, Biology, MESH: Phenotype, MESH: Bone Marrow Neoplasms, Dioxygenases, 03 medical and health sciences, Proto-Oncogene Proteins, medicine, Humans, Family, Genetic Predisposition to Disease, Myelofibrosis, MESH: Family, Myeloproliferative neoplasm, Aged, 030304 developmental biology, Myeloproliferative Disorders, MESH: Humans, Essential thrombocythemia, Myelodysplastic syndromes, MESH: Adult, Cell Biology, medicine.disease, MESH: Male, MESH: Proto-Oncogene Proteins, Cancer research, Bone Marrow Neoplasms, MESH: Female, MESH: DNA-Binding Proteins
Abstract: The JAK2V617F mutation does not elucidate the phenotypic variability observed in myeloproliferative neoplasm (MPN) families. A putative tumor suppressor gene, TET2, was recently implicated in MPN and myelodysplastic syndromes through the identification of acquired mutations affecting hematopoietic stem cells. The present study analyzed the TET2 gene in 61 MPN cases from 42 families. Fifteen distinct mutations were identified in 12 (20%) JAK2V617F-positive or -negative patients. In a patient with 2 TET2 mutations, the analysis of 5 blood samples at different phases of her disease showed the sequential occurrence of JAK2V617F and TET2 mutations concomitantly to the disease evolution. Analysis of familial segregation confirmed that TET2 mutations were not inherited but somatically acquired. TET2 mutations were mainly observed (10 of 12) in patients with primary myelofibrosis or patients with polycythemia vera or essential thrombocythemia who secondarily evolved toward myelofibrosis or acute myeloid leukemia.
Published: 2009
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42. Regulation of DNA Polymerase β by the LMP1 Oncoprotein of EBV through the Nuclear Factor-κB Pathway

Author: Christophe Cazaux, Gauthier Goormachtigh, Jean Coll, Nathalie Faumont, Fabienne Meggetto, Christophe Le Clorennec, Pierre Brousset, Georges Delsol, Jean-Sébastien Hoffmann, Pierre Teira, Jean Feuillard, Yvan Canitrot, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), inconnu, Inconnu, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, P50, DNA polymerase, Molecular Sequence Data, Electrophoretic Mobility Shift Assay, DNA polymerase beta, medicine.disease_cause, Viral Matrix Proteins, Mice, 03 medical and health sciences, Transduction (genetics), chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Electrophoretic mobility shift assay, Binding site, DNA Polymerase beta, Cell Line, Transformed, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Base Sequence, biology, NF-kappa B, DNA, Epstein–Barr virus, Molecular biology, 3. Good health, Enzyme Activation, Enzyme, Oncology, chemistry, 030220 oncology & carcinogenesis, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: The repair DNA polymerase β (Polβ), when overexpressed, plays a critical role in generating genetic instability via its interference with the genomic replication program. Up-regulation of Polβ has been reported in many tumor types that exhibit genetic aberrations, including EBV-related B-cell lymphomas. However, the mechanisms responsible for its overexpression have never been examined. Here, we report that both expression and activity of Polβ, in EBV-immortalized B cells, are induced by several natural genetic variants of LMP1, an oncoprotein associated with the vast majority of EBV-related tumors. Conversely, we found that the expression of Polβ decreased when LMP1 signaling was down-regulated by a dominant negative of LMP1 or an inhibitor of the nuclear factor-κB (NF-κB) pathway, the main transduction pathway activated by LMP1, strongly supporting a role of NF-κB in the LMP1-mediated Polβ regulation. Using electrophoretic mobility shift assay experiments from several EBV-immortalized B-cell nuclear extracts, we identified an LMP1-dependent p50/c-Rel heterodimer on a proximal κB binding site (−211 to −199nt) of the Polβ promoter. This result was correlated with a specific Polβ κB transcriptional activity. Taken together, our data enlighten a new mechanism responsible for Polβ overexpression in EBV-infected cells, mediated by LMP1 and dependent on NF-κB activation. [Cancer Res 2009;69(12):5177–85]
Published: 2009
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43. Ig Synthesis and Class Switching Do Not Require the Presence of the hs4 Enhancer in the 3′ IgH Regulatory Region

Author: Michel Cogné, Véronique Truffinet, Christelle Vincent-Fabert, Yves Denizot, Rémi Fiancette, Nadine Cogné, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Université de Limoges (UNILIM)
Subjects: MESH: Immunoglobulins, MESH: Spleen, Immunology, Immunoglobulins, chemical and pharmacologic phenomena, Regulatory Sequences, Nucleic Acid, MESH: Mice, Knockout, Mice, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), MESH: B-Lymphocytes, MESH: Regulatory Sequences, Nucleic Acid, Animals, Immunology and Allergy, MESH: Animals, Secretion, Enhancer, MESH: Mice, 030304 developmental biology, Mice, Knockout, Genetics, B-Lymphocytes, 0303 health sciences, biology, Immunoglobulin Class Switching, Isotype, MESH: Immunoglobulin M, In vitro, Cell biology, Enhancer Elements, Genetic, Immunoglobulin M, Immunoglobulin class switching, MESH: Immunoglobulin Class Switching, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin heavy chain, MESH: Enhancer Elements, Genetic, Antibody, Immunoglobulin Heavy Chains, Spleen, MESH: Immunoglobulin Heavy Chains, 030215 immunology
Abstract: Several studies have reported that regulatory elements located 3′ of the IgH locus (namely hs3a, hs1,2, hs3b, and hs4) might play a role during class switch recombination (CSR) and Ig synthesis. While individual deletion of hs3a or hs1,2 had no effect, pairwise deletion of hs3b (an inverted copy of hs3a) and hs4 markedly affected CSR and Ig expression. Among these two elements, hs4 was tentatively presented with the master role due to its unique status within the 3′ regulatory region: distal position outside repeated regions, early activation in pre-B cells, strong activity throughout B cell ontogeny. To clarify its role, we generated mice with a clean deletion of the hs4 after replacement with a floxed neoR cassette. Surprisingly, and as for previous deletion of hs3a or hs1,2, deletion of hs4 did not affect either in vivo CSR or the secretion level of any Ig isotype. In vitro CSR and Ig secretion in response to LPS and cytokines was not affected either. The only noticeable effects of the hs4 deletion were a decrease in the number of B splenocytes and a decreased membrane IgM expression. In conclusion, while dispensable for CSR and Ig transcription in plasma cells, hs4 mostly appears to contribute to Ig transcription in resting B lymphocytes.
Published: 2009
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44. The favorable impact of CEBPA mutations in patients with acute myeloid leukemia is only observed in the absence of associated cytogenetic abnormalities and FLT3 internal duplication

Author: Xavier Thomas, Olivier Nibourel, Nicolas Boissel, Aline Renneville, Nathalie Gachard, Dina Naguib, Stéphane de Botton, Hervé Dombret, Oumedaly Reman, Christian Bastard, Claude Gardin, Claude Preudhomme, Christine Terré, Sylvie Castaigne, Cécile Pautas, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de génétique oncologique, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Versailles André Mignot (CHV), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Oncology, Biochemistry, 0302 clinical medicine, Recurrence, Gene Duplication, hemic and lymphatic diseases, Enhancer binding, Gene duplication, CEBPA, MESH: CCAAT-Enhancer-Binding Protein-alpha, MESH: Treatment Outcome, MESH: Aged, 0303 health sciences, Acute leukemia, MESH: Middle Aged, MESH: Gene Duplication, Hazard ratio, Myeloid leukemia, Hematology, Middle Aged, Prognosis, 3. Good health, Survival Rate, Leukemia, Myeloid, Acute, Treatment Outcome, MESH: Young Adult, 030220 oncology & carcinogenesis, Chromosome abnormality, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Leukemia, Myeloid, Acute, MESH: fms-Like Tyrosine Kinase 3, Adult, medicine.medical_specialty, MESH: Mutation, MESH: Survival Rate, Adolescent, Immunology, Context (language use), Biology, MESH: Prognosis, Disease-Free Survival, Young Adult, 03 medical and health sciences, Internal medicine, CCAAT-Enhancer-Binding Protein-alpha, medicine, MESH: Chromosome Aberrations, Humans, Aged, 030304 developmental biology, MESH: Adolescent, Chromosome Aberrations, MESH: Humans, MESH: Adult, Cell Biology, medicine.disease, MESH: Male, MESH: Recurrence, fms-Like Tyrosine Kinase 3, MESH: Disease-Free Survival, Mutation, Cancer research, MESH: Female
Abstract: Mutations of the CCAAT/enhancer binding protein alpha (CEBPA) gene have been associated with a favorable outcome in patients with acute myeloid leukemia (AML), but mainly in those with a normal karyotype. Here, we analyzed the impact of associated cytogenetic abnormalities or bad-prognosis fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in 53 patients with CEBPA+ de novo AML treated in the Acute Leukemia French Association trials. We found that only those with a normal karyotype and no FLT3-ITD displayed the expected favorable outcome. In this context, relapse-free, disease-free, and overall survival were significantly longer than in corresponding patients without the CEBPA mutation (P = .035, .016, and .047, respectively). This was not observed in the context of an abnormal karyotype or associated FLT3-ITD. Furthermore, after adjustment on age, trial, and mutation type, these features were independently predictive of shorter overall survival in the subset of patients with CEBPA+ AML (multivariate hazard ratio = 2.7; 95% confidence interval, 1.08-6.7; and 2.9; 95% confidence interval, 1.01-8.2; with P = .034 and .05, for abnormal karyotype and FLT3-ITD, respectively).
Published: 2009
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45. Glycaemic control in type 2 diabetic patients on chronic haemodialysis: use of a continuous glucose monitoring system

Author: Jean-Pierre Riveline, Franck Bridoux, Guillaume Charpentier, Samy Hadjadj, Valérie Caudwell, Simohamed Belmouaz, Richard Marechaud, Julie Teynie, Dured Dardari, Marc Bauwens, Sylvia Franc, Stéphanie Ragot, Service Endocrinologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Service de Diabétologie, Hôpital Sud Francilien Corbeil Essonne, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Corbeil, Ischémie - Reperfusion en transplatation rénale, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM CIC802 (CIC802), and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Blood Glucose, Male, medicine.medical_treatment, 030232 urology & nephrology, Type 2 diabetes, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Diabetic Nephropathies, MESH: Renal Dialysis, MESH: Aged, MESH: Middle Aged, Glucose meter, Middle Aged, 3. Good health, Fructosamine, Nephrology, MESH: Hemoglobin A, Glycosylated, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Hemodialysis, MESH: Diabetes Mellitus, Type 2, medicine.medical_specialty, MESH: Diabetic Nephropathies, 030209 endocrinology & metabolism, MESH: Blood Glucose Self-Monitoring, 03 medical and health sciences, Renal Dialysis, Diabetes mellitus, Internal medicine, medicine, Humans, Dialysis, Aged, Glycated Hemoglobin, Transplantation, MESH: Humans, business.industry, Blood Glucose Self-Monitoring, MESH: Fructosamine, medicine.disease, MESH: Male, Endocrinology, Diabetes Mellitus, Type 2, chemistry, MESH: Blood Glucose, Hemoglobin, business, MESH: Female, Kidney disease
Abstract: International audience; BACKGROUND: The proportion of diabetic patients undergoing haemodialysis is rapidly increasing. Glucose control among such patients is difficult to assess. We aimed to evaluate the clinical performance of a continuous glucose monitoring system (CGMS) in type 2 diabetic patients on chronic haemodialysis. METHODS: We used a 4-day CGMS to monitor glucose levels in 19 haemodialysed type 2 diabetic patients (HD T2) including 2 days with and 2 days without dialysis session, and 39 non-HD T2 in a double-centre study. RESULTS: The glucose concentration according to the glucose meter and CGMS were correlated in HD T2 patients (r = 0.90, P < 0.0001) and in non-HD T2 patients (r = 0.81, P < 0.0001). The relative absolute difference (RAD) between glucose determined by a glucose meter and glucose determined by the CGMS did not differ between HD T2 and non-HD T2 patients (9.2 +/- 10.5 vs. 8.2 +/- 7.6%; P = 0.165). Glycated haemoglobin (A1c) and mean glucose concentration were strongly correlated in non-HD T2 patients (r = 0.71; P < 0.0001) but weakly correlated in HD T2 patients (r = 0.47; P = 0.042). Fructosamine was correlated with the mean glucose concentration in non-HD T2 (r = 0.67; P < 0.0001) but not in HD T2 patients (r = 0.04; P = 0.88). CONCLUSION: CGM is a validated marker of glycaemic control in HD diabetic patients. This tool showed that A1c and fructosamine, despite being good markers of glycaemic control in non-HD diabetic patients, are of poor value in HD diabetic patients.
Published: 2009
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46. Among 157 marginal zone lymphomas, DBA.44(CD76) expression is restricted to tumour cells infiltrating the red pulp of the spleen with a diffuse architectural pattern

Author: Nathalie Gachard, Dominique Bordessoule, Abdelghafour Marfak, Marie Parrens, Isabelle Soubeyran, Jean Feuillard, François Labrousse, Valérie Costes-Martineau, Mélanie Boulin, Camille Laurent, Barbara Petit, Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Neurologie - Côte Basque (NEUROLOGIE), Hopital, Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mathématiques d'Orsay (LM-Orsay), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Service de Neurologie [CHU Limoges], Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], and Université de Limoges (UNILIM)
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Histology, MESH: Spleen, Spleen, Biology, Pathology and Forensic Medicine, 03 medical and health sciences, MESH: Aged, 80 and over, 0302 clinical medicine, Architectural pattern, Antigens, CD, Biomarkers, Tumor, medicine, Humans, MESH: Lymphoma, B-Cell, Marginal Zone, MESH: Antigens, CD, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Humans, MESH: Middle Aged, MESH: Adult, Lymphoma, B-Cell, Marginal Zone, General Medicine, Middle Aged, Marginal zone, MESH: Male, medicine.anatomical_structure, Expression (architecture), 030220 oncology & carcinogenesis, MESH: Tumor Markers, Biological, Immunology, Red pulp, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Female
Abstract: International audience
Published: 2009
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47. Uncoupling between Ig somatic hypermutation and oncogene mutation in mouse lymphoma

Author: Yves Denizot, Rémi Fiancette, Barbara Petit, Nadine Cogné, Christelle Vincent, Michel Cogné, Véronique Truffinet, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Université de Limoges (UNILIM)
Subjects: Anaplastic Lymphoma, Lymphoma, 5' Flanking Region, 5' flanking region, DNA Mutational Analysis, Molecular Sequence Data, Genes, myc, Immunoglobulin Variable Region, Somatic hypermutation, Mice, Transgenic, Biology, 03 medical and health sciences, Exon, Mice, 0302 clinical medicine, medicine, Animals, RNA, Messenger, Cell activation, Gene, Molecular Biology, B cell, Locus control region, 030304 developmental biology, Genetics, 0303 health sciences, Gene Expression Profiling, Exons, Cell Biology, Locus Control Region, Burkitt Lymphoma, Gene regulation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mutation, Proto-Oncogene Proteins c-bcl-6, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin heavy chain, Somatic Hypermutation, Immunoglobulin, Immunoglobulin Heavy Chains
Abstract: International audience; Burkitt lymphoma (BL) features translocations linking c-myc to the immunoglobulin heavy chain (IgH) locus. By inserting a c-myc gene under the control of the 3'IgH locus control region (LCR) into the mouse genome, we generated c-myc-3'LCR mice that develop clonal BL or diffuse anaplastic lymphoma. We show in the present study that while BL from c-myc-3'LCR mice would be classified as pre-germinal center (GC) cells due to the absence of both BCL-6 expression and somatic hypermutation (SHM) in V(H) sequences, they show a high level of SHM focused on the c-myc oncogene itself. This observation suggests that the c-myc-3'IgH LCR tandem association drives development of lymphoma from na? B cells by specifically recruiting AID activity on c-myc in a process that early becomes independent from antigen selection and where the successive rounds of SHM rather rely on the selection of the most efficient mutations for oncogene deregulation. Similar to the translocated c-myc gene in human BL, mutations were found in first exon and 5' flanking sequences of transgenic c-myc and specially focused on negative regulatory elements, thus leading to high and constitutive oncogene expression. In conclusion while 3'IgH transcriptional enhancers in c-myc-3'LCR mice first simply act in cis to slightly stimulate c-myc transcription in untransformed B cells, the occurrence of lymphoma appears to result from an additional mechanism necessitating AID-driven mutations within the first exon and 5' flanking sequences which does not occur in parallel but rather circumvents antigen-driven selection.
Published: 2009
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48. Increased cyclooxygenase-2 and thromboxane synthase expression is implicated in diosgenin-induced megakaryocytic differentiation in human erythroleukemia cells

Author: Serge Battu, Clementine Cailleteau, Bertrand Liagre, Chantal Jayat-Vignoles, Jean-Louis Beneytout, Biomolécules Thérapies anti-tumorales (EA4021), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université de Limoges (UNILIM), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Platelet Membrane Glycoprotein IIb, MESH: Cyclooxygenase 2 Inhibitors, Cellular differentiation, Biochemistry, MESH: Ploidies, chemistry.chemical_compound, 0302 clinical medicine, MESH: Animals, 0303 health sciences, biology, MESH: Dinoprostone, Cell Differentiation, MESH: Gene Expression Regulation, Neoplastic, Diosgenin, MESH: Diosgenin, Fractionation, Field Flow, Cell biology, MESH: Megakaryocytes, Gene Expression Regulation, Neoplastic, MESH: Cattle, Haematopoiesis, Leukemia, MESH: Thromboxane-A Synthase, 030220 oncology & carcinogenesis, Thromboxane-A Synthase, MESH: Cyclooxygenase 2, MESH: Leukemia, Erythroblastic, Acute, Megakaryocytes, MESH: Cell Differentiation, Platelet Membrane Glycoprotein IIb, MESH: Cell Line, Tumor, Biophysics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dinoprostone, MESH: Microsomes, 03 medical and health sciences, Cell Line, Tumor, Microsomes, medicine, Animals, Humans, Molecular Biology, 030304 developmental biology, MESH: Humans, Ploidies, Cyclooxygenase 2 Inhibitors, MESH: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, Cell Biology, MESH: Fractionation, Field Flow, medicine.disease, chemistry, Cyclooxygenase 2, Apoptosis, 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, biology.protein, Cattle, Leukemia, Erythroblastic, Acute, Cyclooxygenase, Thromboxane-A synthase, Function (biology)
Abstract: International audience; Differentiation induction as a therapeutic strategy has, so far, the greatest impact in hematopoietic malignancies, most notably leukemia. Diosgenin is a very interesting natural product because, depending on the specific dose used, its biological effect is very different in HEL (human erythroleukemia) cells. For example, at 10 microM, diosgenin induced megakaryocytic differentiation, in contrast to 40 microM diosgenin, which induced apoptosis in HEL cells previously demonstrated using sedimentation field-flow fractionation (SdFFF). The goal of this work focused on the correlation between cyclooxygenase-2 (COX-2) and thromboxane synthase (TxS) and megakaryocytic differentiation induced by diosgenin in HEL cells. Furthermore, the technique of SdFFF, having been validated in our models, was used in this new study as an analytical tool that provided us with more or less enriched differentiated cell fractions that could then be used for further analyses of enzyme protein expression and activity for the first time. In our study, we showed the implication of COX-2 and TxS in diosgenin-induced megakaryocytic differentiation in HEL cells. Furthermore, we showed that the analytical technique of SdFFF may be used as a tool to confirm our results as a function of the degree of cell differentiation.
Published: 2008
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49. Multicenter study of ZAP-70 expression in patients with B-cell chronic lymphocytic leukemia using an optimized flow cytometry method

Author: Gachard, Nathalie, Salviat, Aurélie, Boutet, Catherine, Arnoulet, Christine, Durrieu, Françoise, Lenormand, Bernard, Leprêtre, Stéphane, Olschwang, Sylviane, Jardin, Fabrice, Lafage-Pochitaloff, Marina, Penther, Dominique, Sainty, Danielle, Reminieras, Liliane, Feuillard, Jean, Béné, Marie C, Renseigné, Non, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [CHU Dupuytren], Hôpital Dupuytren [CHU Limoges], Laboratoire d'hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Bergonié [Bordeaux], UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Cancérologie (Inserm U599/IPC), Université de la Méditerranée - Aix-Marseille 2-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncologie Génétique [Rouen] (CLCC Henri Becquerel), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'Immunologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Carrion, Claire, Division Physico-chimie des Matériaux (LCPC/PCM), Laboratoire Central des Ponts et Chaussées (LCPC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Oncology, Pathology, Chronic lymphocytic leukemia, MESH: Membrane Glycoproteins, Immunoglobulin Variable Region, MESH: Immunoglobulin Variable Region, Blood Donors, Trisomy, MESH: Flow Cytometry, CD38, 0302 clinical medicine, MESH: Leukemia, Lymphocytic, Chronic, B-Cell, Membrane Glycoproteins, ZAP-70 Protein-Tyrosine Kinase, Hematology, medicine.diagnostic_test, Gene Expression Regulation, Leukemic, hemic and immune systems, Flow Cytometry, Prognosis, Leukemia, 030220 oncology & carcinogenesis, MESH: Gene Expression Regulation, Leukemic, MESH: Trisomy, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Chromosome Deletion, Immunoglobulin Heavy Chains, MESH: Immunoglobulin Heavy Chains, medicine.medical_specialty, MESH: Mutation, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Chromosome Deletion, chemical and pharmacologic phenomena, Peripheral blood mononuclear cell, MESH: Prognosis, Flow cytometry, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Chromosomes, Human, Pair 12, MESH: Humans, business.industry, Chromosomes, Human, Pair 11, MESH: Antigens, CD38, MESH: Blood Donors, Cancer, MESH: ZAP-70 Protein-Tyrosine Kinase, medicine.disease, ADP-ribosyl Cyclase 1, Leukemia, Lymphocytic, Chronic, B-Cell, MESH: Male, Mutation, MESH: Tumor Markers, Biological, MESH: Chromosomes, Human, Pair 12, MESH: Chromosomes, Human, Pair 11, business, MESH: Female, 030215 immunology
Abstract: International audience; BACKGROUND: Flow cytometry allows specific assessment of the expression of ZAP-70, a promising new prognostic factor in B-cell chronic lymphocytic leukemia (B-CLL), but suffers from a lack of multicenter standardization. DESIGN AND METHODS: An optimized method for direct detection of ZAP-70 in flow cytometry was tested in a multicenter fashion. Adapted for frozen cells, this method includes a normalization step by addition of B cells from a pool of peripheral blood mononuclear cells collected from normal donors. ZAP-70 expression levels were assessed for 153 patients with typical B-cell chronic lymphocytic leukemia chronic lymphocytic leukemia. Results were expressed as the ratio of ZAP-70 mean fluorescence intensity between B-CLL cells and normal B cells. RESULTS: The statistically optimized cut-off of ZAP-70 positivity was a ratio of 1.4. Concordance between ZAP-70 and CD38 expression was 67%. Concordance between the mutational status of IgVH genes and ZAP-70 or CD38 expression was 87% and 65%, respectively. ZAP-70 was significantly expressed in 28%, 54% and 61% of patients with Binet stages A, B and C B-cell chronic lymphocytic leukemia, respectively (p=0.008). The absence of ZAP-70 expression was associated with isolated del(13q14), a cytogenetic abnormality with a good prognosis, while most patients with the del(17p13) poor prognosis cytogenetic marker expressed ZAP-70 (p
Published: 2008
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50. Sequential activation and distinct functions for distal and proximal modules within the IgH 3′ regulatory region

Author: Marie Marquet, Frederick W. Alt, Zeliha Oruc, Armand Garot, Michel Cogné, Claire Carrion, Sandrine Le Noir, Alexis Saintamand, Eric Pinaud, Kevin Lebrigand, Anne-Gaëlle Bébin, Sébastien Bender, Yves Denizot, Jeanne Moreau, Pauline Rouaud, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Handicap et système nerveux :Action, communication, interaction: rétablissement de la fonction et de la participation [Bordeaux] (EA4136), UFR Sciences médicales 3 [Bordeaux]-Université de Bordeaux Ségalen [Bordeaux 2], Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Université Nice Sophia Antipolis (... - 2019) (UNS), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Heterozygote, Transcription, Genetic, Receptor expression, Mutant, Receptors, Antigen, B-Cell, Somatic hypermutation, Cell Count, Regulatory Sequences, Nucleic Acid, Biology, Plasma cell, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Antigen, Transcription (biology), medicine, Animals, Cell Lineage, RNA, Antisense, RNA, Messenger, Antigens, ComputingMilieux_MISCELLANEOUS, Sequence Deletion, Mice, Knockout, B-Lymphocytes, Multidisciplinary, Biological Sciences, Flow Cytometry, Germinal Center, Immunoglobulin Class Switching, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Immunoglobulin M, Immunoglobulin class switching, Antibody Formation, Gene Targeting, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Somatic Hypermutation, Immunoglobulin, Antibody, Immunoglobulin Heavy Chains, 030215 immunology
Abstract: Significance The immunoglobulin heavy chain (IgH) 3′regulatory region ( 3′RR ) fine-tunes IgH gene expression during B cell development. One singularity of this region is its quasi-palindromic structure conserved in the 3′RR of other species. By comparing previous mouse knockout (KO) models ( 3′RR- and hs3b-4 KO) to a novel mutant devoid of the quasi-palindrome ( 3′PAL KO), we highlighted common features and differences that specify two distinct regulatory entities: ( i ) the distal module ( hs4 ) is sufficient for normal IgH expression up to the naïve B cell stage; ( ii ) during B-cell activation, the proximal module (quasi-palindrome) is important for both class switch recombination and somatic hypermutation; and ( iii ) in plasma cells, the quasi-palindrome is required for robust transcription of the IgH locus.
Published: 2016
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