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1. Improvement of Standardization of Molecular Analyses in Hematology: The 10-year GBMHM French Experience

Author

Damien Luque-Paz, Sandrine Hayette, Anne Sophie Alary, Jean Michel Cayuela, Claude Preudhomme, Olivier Kosmider, Elizabeth Macintyre, Fanny Baran-Marszak, Marie Hélène Delfau-Larue, Carole Mauté, Bruno Cassinat, Pascale Flandrin-Gresta, Frederic Davi, Eric Lippert, Pierre Sujobert, Audrey Gauthier, Pascale Cornillet-Lefebvre, Gestionnaire, HAL Sorbonne Université 5, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), [Institut Cochin] Département Développement, Reproduction et Cancer (DRC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], 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), Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 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), and 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)

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Standardization, Article, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Retrospective analysis, medicine, Diseases of the blood and blood-forming organs, Medical physics, Accreditation, business.industry, International standard, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Objective Improvement, 3. Good health, Test (assessment), 030220 oncology & carcinogenesis, RC633-647.5, business, JAK2 V617F, Quality assurance, 030215 immunology
Abstract

International audience; Molecular tests have become an indispensable tool for the diagnosis and prognosis of hematological malignancies and are subject to accreditation according to the International Standard ISO 15189. National standardization of these techniques is essential to ensure that patients throughout France benefit from the same care. We report here on the experience of the GBMHM (Groupe des Biologistes Moléculaires des Hémopathies Malignes). By organizing External Evaluation of Quality (EEQ) programs and training meetings, the GBMHM has contributed to improvement and standardization of molecular tests in 64 French laboratories. A retrospective analysis of the quality-control results of 11 national campaigns spanning 10 years was performed for the 3 most frequently prescribed tests: BCR-ABL1, JAK2 V617F, and lymphoid clonality. For each test, particular attention was placed on comparing methodologies and their evolution throughout the period. The establishment of the BCR-ABL1, JAK2 V617F, and lymphoid clonality EEQ programs and the associated training meetings have initiated a process of collective standardization concerning the methods of implementation (JAK2 V617F) and the interpretation and formulation of results (lymphoid clonality). In addition, it resulted in objective improvement in technical performance (BCR-ABL1). Our evaluation of the impact of these EEQ programs demonstrates that it is possible to obtain reproducible values across different laboratories in France by applying national recommendations. To our knowledge, this is the first publication that evaluates the impact of a national quality assurance program on improving molecular results in hematology.

Published
2021
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2. Influence of major BCR-ABL1 transcript subtype on outcome in patients with chronic myeloid leukemia in chronic phase treated frontline with nilotinib

Author

Nadine Cadoux, Alexandre Janel, Françoise Huguet, Franck E. Nicolini, Marc G. Berger, Pascale Flandrin-Gresta, Sandrine Hayette, Sandrine Saugues, Pascale Cohny-Makhoul, Denis Guyotat, Carole Colin-Gil, Lydia Campos, Alexis Genthon, Jean-Michel Cayuela, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, medicine.drug_class, Chromosomal translocation, Chromosome 9, Tyrosine-kinase inhibitor, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Myeloproliferative neoplasm, ComputingMilieux_MISCELLANEOUS, business.industry, Myeloid leukemia, Imatinib, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, 3. Good health, 030104 developmental biology, Nilotinib, 030220 oncology & carcinogenesis, Relative risk, business, medicine.drug
Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of BCR-ABL1 transcript as a result of reciprocal translocation between chromosome 9 and 22. The most common transcripts subtypes are e13a2 (b2a2) and e14a2 (b3a2). The prognostic impact of the type of BCR-ABL1 transcript has been the subject of controversies over time. In the imatinib era, several studies have suggested a deeper and faster response in patients expressing e14a2. However, the impact on response after first line therapy with a second-generation tyrosine kinase inhibitor, nilotinib, is unknown. We retrospectively evaluated 118 patients newly diagnosed with chronic phase CML and treated frontline with nilotinib inside or outside clinical trial in five French centers. Only patients expressing e14a2 or e13a2 transcripts alone were analyzed. At baseline, 55.3% expressed e14a2, 44.7% expressed e13a2. The median age was 51 years and median follow-up was 49 months. Relative risks of CML at diagnosis were similar according to the ELTS score (p = .87). Complete hematological response and complete cytogenetic response rates were similar among groups. Patients expressing e14a2 transcripts compared to e13a2 transcripts had deeper and faster molecular responses, when considering MMR (100% vs 84.1%, p = .007) with a median time of 6.7 and 17.1 months or MR4.5 (100% vs 59.9%, p = .005) with a median time of 39.7 and 70.9 months, respectively. A sustained treatment free remission was observed in 10/10 patients with e14a2 versus 1/3 with e13a2 transcript (p = .04). In conclusion, even treated with nilotinib first line, patients with chronic phase CML expressing BCR-ABL1 e13a2 transcript have a lower rate of deep molecular responses.

Published
2020
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3. Genetic analysis of therapy-related myeloid neoplasms occurring after intensive treatment for acute promyelocytic leukemia

Author

Eric Delabesse, Sandrine Hayette, Lionel Ades, Sophie Park, Virginie Eclache, Bruno Cassinat, Cecile Bally, Aline Renneville, Xavier Thomas, Jean Feuillard, Philippe Attias, Pierre Fenaux, Julie Lejeune, Hassan Farhat, Christine Terré, Claude Preudhomme, Alice Marceau-Renaut, Sylvie Chevret, Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sciences Po Grenoble - Institut d'études politiques de Grenoble (IEPG), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie Hôpital Mignot, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier de Versailles André Mignot (CHV), Service d'hématologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-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], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Avicenne, 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), CHU Versailles, Centre Hospitalier de Versailles (CHV), CHU Necker - Enfants Malades [AP-HP]-Centre National de la Recherche Scientifique (CNRS), 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), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), 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), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)

Subjects
Acute promyelocytic leukemia, Adult, Cancer Research, Myeloid, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Bioinformatics, Genetic analysis, 03 medical and health sciences, 0302 clinical medicine, Leukemia, Promyelocytic, Acute, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetic variation, Antineoplastic Combined Chemotherapy Protocols, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Humans, Genetic Testing, Allele, Alleles, ComputingMilieux_MISCELLANEOUS, Genetic testing, medicine.diagnostic_test, Radiotherapy, business.industry, Genetic Variation, Neoplasms, Second Primary, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, 3. Good health, Radiation therapy, medicine.anatomical_structure, Oncology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Mutation, business, Biomarkers, 030215 immunology
Abstract

International audience

Published
2018
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4. Splenic diffuse red pulp lymphoma has a distinct pattern of somatic mutations amongst B-cell malignancies

Author

Françoise Berger, Pascale Felman, Sandrine Hayette, Martine Ffrench, Laurent Jallades, Bertrand Coiffier, Evelyne Callet-Bauchu, Kaddour Chabane, Aurélie Verney, Sophie Gazzo, Gilles Salles, Alexandra Traverse-Glehen, Lucile Baseggio, Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, Hospices Civils de Lyon ( HCL ), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Cancer Research, Pathology, Lymphoma, diagnosis, DNA Mutational Analysis, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Immunophenotyping, Lymphocytes, In Situ Hybridization, Fluorescence, Aged, 80 and over, Mutation, Hematology, Middle Aged, Immunohistochemistry, 3. Good health, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Red pulp, Female, France, IGHV@, medicine.medical_specialty, Lymphoma, B-Cell, Patients, Cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, Splenic Neoplasm, Biology, 03 medical and health sciences, Antigens, CD, blood, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, B cell, Aged, Neoplasm Staging, Retrospective Studies, Chromosome Aberrations, Splenic Neoplasms, medicine.disease, Lymph Nodes, Splenic Lymphoma, 030215 immunology
Abstract

International audience; Splenic Diffuse Red Pulp Lymphoma (SDRPL) has been recently introduced as a provisional entity but differential diagnosis with other splenic lymphomas is needed to be clarified since the therapeutic approaches are distinct. Recently described recurrent mutations or CD180 expression appear useful for differential diagnosis. We completed our previous description in a larger cohort including 53 patients selected on the presence of characteristic villous cells in peripheral blood (PB) and a specific immunophenotype. Immunoglobulin heavy variable (IGHV), BRAF, MYD88, and NOTCH2 mutations were determined and CD180 and BRAF expressions were assessed. Most cases (79%) were IGHV mutated with an overrepresentation of IGHV3-23 (19%) and IGHV4-34 (21%). MYD88 L265P and NOTCH2 mutations were observed in one case each, whereas no BRAF V600E mutation or expression was found. All cases demonstrated a high CD180 expression. Those results strengthen the concept that SDRPL does emerge as a new lymphoma entity distinct from the other splenic lymphomas with circulating lymphocytes

Published
2017
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5. Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: a GRAALL study

Author

Marie-Christiane Vekemans, Martine Escoffre, Norbert Ifrah, Hervé Dombret, Delphine Rea, Aline Tanguy-Schmidt, Xavier Thomas, Sandrine Hayette, Philippe Rousselot, André Delannoy, Yves Chalandon, Jean-Paul Vernant, Jean-Yves Cahn, Françoise Huguet, Jean-Michel Cayuela, Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Laboratoire central d'hématologie, 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 Diderot - Paris 7 (UPD7), Laboratoire de Biologie Moléculaire, Hospices Civils de Lyon (HCL), 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], Hôpital de Jolimont, Haine-Saint-Paul and Cliniques Universitaires St Luc, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Hôpital Edouard Herriot [CHU - HCL]

Subjects
Oncology, Male, Time Factors, medicine.medical_treatment, MESH: Piperazines, Hematopoietic stem cell transplantation, Acute lymphoblastic leukemia, MESH: Philadelphia Chromosome, Piperazines, MESH: Unrelated Donors, MESH: Benzamides, 0302 clinical medicine, hemic and lymphatic diseases, Philadelphia Chromosome, ddc:616, Philadelphia Chromosome Positive, MESH: Middle Aged, Stem cell transplantation, Age Factors, Hematopoietic Stem Cell Transplantation, Hematology, MESH: Follow-Up Studies, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Transplantation, Autologous, 3. Good health, Survival Rate, Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality/therapy, 030220 oncology & carcinogenesis, Benzamides, Imatinib Mesylate, Female, Unrelated Donors, medicine.drug, Adult, medicine.medical_specialty, Adolescent, MESH: Survival Rate, Pyrimidines/administration & dosage/adverse effects, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Philadelphia chromosome, Transplantation, Autologous, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Survival rate, MESH: Hematopoietic Stem Cell Transplantation, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Age Factors, Transplantation, MESH: Humans, business.industry, MESH: Time Factors, Imatinib, Benzamides/administration & dosage/adverse effects, MESH: Adult, medicine.disease, Piperazines/administration & dosage/adverse effects, MESH: Male, Surgery, Clinical trial, Imatinib mesylate, Pyrimidines, MESH: Pyrimidines, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, Antineoplastic Agents/administration & dosage/adverse effects, business, MESH: Female, 030215 immunology, Follow-Up Studies
Abstract

International audience; We report here the results of the GRAAPH-2003 trial with long-term follow-up in 45 patients with de novo Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib-based strategy improved the 4-year overall survival (OS) up to 52% versus 20% in the pre-imatinib LALA-94 trial (P = .0001). Despite the selection in patients who actually underwent transplantation, these results suggest that allogeneic or autologous stem cell transplants (SCTs) still have a place in overcoming the poor prognosis of Ph+ ALL in the era of imatinib therapy. OS was 50% after allogeneic SCT (24 patients), 33% in patients without a transplantation (9 patients), and 80% after autologous SCT (10 patients without allogeneic donor or >55 years, including 7 patients in complete molecular response).

Published
2013
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6. Early immune reconstitution and efficient graft vs tumor effect after unrelated partially matched double cord blood transplantation in refractory 8p11 syndrome

Author

Sandrine Hayette, Pierre-Simon Rohrlich, Christophe Ferrand, Fabienne Pouthier, Fabrice Larosa, Pierre Tiberghien, Philippe Saas, Faezeh Legrand, Jacqueline Chabod, Stéphane Maddens, Eric Deconinck, Saas, Philippe, Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), EFS Rhône-Alpes, EFS, Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), 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 [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire de Biologie Moléculaire, Hospices Civils de Lyon (HCL), Laboratoire HLA, Service d'hématologie pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])

Subjects
medicine.medical_specialty, Pathology, [SDV.IMM] Life Sciences [q-bio]/Immunology, Umbilical cord, Blood cell, 03 medical and health sciences, 0302 clinical medicine, Immune system, Refractory, Unrelated Donor, Internal medicine, medicine, Cord blood transplantation, ComputingMilieux_MISCELLANEOUS, Transplantation, Hematology, business.industry, 3. Good health, surgical procedures, operative, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, business, 030215 immunology
Abstract

Early immune reconstitution and efficient graft vs tumor effect after unrelated partially matched double cord blood transplantation in refractory 8p11 syndrome

Published
2010
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7. Cloning of the mouse BTG3 gene and definition of a new gene family (the BTG family) involved in the negative control of the cell cycle

Author

Fabienne Guehenneux, R Bouhas, AM Birot, Sandrine Hayette, Jean-Pierre Magaud, Cyril Berthet, Laurent Duret, Q Wang, R Rimokh, Jean-Pierre Rouault, C. Samarut, Mary Callanan, Bioinformatique, phylogénie et génomique évolutive (BPGE), Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université de Lyon-Université de Lyon, Institut de Génomique Fonctionnelle de Lyon (IGFL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cancer Research, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], DNA, Complementary, Tumor suppressor gene, Chromosomes, Human, Pair 21, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Pair-rule gene, Biology, Conserved sequence, 03 medical and health sciences, Mice, 0302 clinical medicine, Gene cluster, Gene family, Animals, Humans, Genes, Tumor Suppressor, Amino Acid Sequence, Cloning, Molecular, Gene, Phylogeny, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetics, 0303 health sciences, BTG2, Base Sequence, Cell Cycle, Hematology, Blotting, Northern, Oncology, 030220 oncology & carcinogenesis, BTG1
Abstract

It is well known that loss of tumor suppressor genes and more generally of antiproliferative genes plays a key role in the development of most tumors. We report here the cloning of the mouse BTG3 gene and show that its human counterpart maps on chromosome 21. This evolutionarily conserved gene codes for a 30 kDa protein and is expressed in most adult murine and human tissues analyzed. However, we demonstrate that its expression is cell cycle dependent and peaks at the end of the G1 phase. This gene is homologous to the human BTG1, BTG2 and TOB genes which were demonstrated to act as inhibitors of cell proliferation. Its description allowed us to define better this seven gene family (the BTG gene family) at the structural level and to speculate about its physiological role in normal and tumoral cells. This family is mainly characterized by the presence of two conserved domains (BTG boxes A and B) of as yet undetermined function which are separated by a non-conserved 20-25 amino acid sequence.

Published
1997
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