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13 results on '"Hélène Lapillonne"'

1. Clonal hematopoiesis driven by chromosome 1q/MDM4 trisomy defines a canonical route toward leukemia in Fanconi anemia

Author

Marie Sebert, Stéphanie Gachet, Thierry Leblanc, Alix Rousseau, Olivier Bluteau, Rathana Kim, Raouf Ben Abdelali, Flore Sicre de Fontbrune, Loïc Maillard, Carèle Fedronie, Valentine Murigneux, Léa Bellenger, Naira Naouar, Samuel Quentin, Lucie Hernandez, Nadia Vasquez, Mélanie Da Costa, Pedro H. Prata, Lise Larcher, Marie de Tersant, Matthieu Duchmann, Anna Raimbault, Franck Trimoreau, Odile Fenneteau, Wendy Cuccuini, Nathalie Gachard, Nathalie Auger, Giulia Tueur, Maud Blanluet, Claude Gazin, Michèle Souyri, Francina Langa Vives, Aaron Mendez-Bermudez, Hélène Lapillonne, Etienne Lengline, Emmanuel Raffoux, Pierre Fenaux, Lionel Adès, Edouard Forcade, Charlotte Jubert, Carine Domenech, Marion Strullu, Bénédicte Bruno, Nimrod Buchbinder, Caroline Thomas, Arnaud Petit, Guy Leverger, Gérard Michel, Marina Cavazzana, Eliane Gluckman, Yves Bertrand, Nicolas Boissel, André Baruchel, Jean-Hugues Dalle, Emmanuelle Clappier, Eric Gilson, Ludovic Deriano, Sylvie Chevret, François Sigaux, Gérard Socié, Dominique Stoppa-Lyonnet, Hugues de Thé, Christophe Antoniewski, Dominique Bluteau, Régis Peffault de Latour, Jean Soulier, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Recherche clinique appliquée à l'hématologie (URP_3518), Intégrité du génome, immunité et cancer - Genome integrity, Immunity and Cancer, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Institut Gustave Roussy (IGR), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Ingénierie génétique murine - Mouse Genetics Engineering Center (CIGM), Institut Pasteur [Paris] (IP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpitaux universitaires Est parisien [AP-HP], CHU Bordeaux [Bordeaux], Hospices Civils de Lyon (HCL), 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), CIC NECKER BT (CIC 1416), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Collège de France (CdF (institution)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), This study received support from the European Research Council (ERC) Consolidator Grant to J.S. (CEVAL-311660), the FP7 Eurofancolen program (HEALTH-F5-2012-305421), the ANR program PACRI (Projet alliance parisienne des instituts de recherche en cancérologie), the CONECT-AML (Collaborative Network for Children and Teenagers with Acute Myeloid Leukemia) program supported by a grant from the Institut National du Cancer (INCa), Fondation ARC, Ligue nationale contre le cancer, and Laurette Fugain (INCa-ARC-LIGUE_11905) to J.S. and C.A., and the Association Française pour la Maladie de Fanconi (AFMF) grants 'Histoire naturelle de la maladie de Fanconi' to R.P.L. and J.S., 'Modélisation de la transformation leucémique dans la maladie de Fanconi' to D.B., and 'Cribles fonctionnels à haut débit de gènes modificateurs de la maladie de Fanconi' to C.G. M.S. was supported by the AVIESAN-INCa Program 'Formation à la Recherche Translationnelle,' and A.R. by a grant from the Fondation ARC. The work in E.G.’s lab is supported by Fondation ARC and ANR Telochrom. The work in L.D.’s lab is supported by INCa (PLBIO16-181) and ERC (310917)., ANR-11-PHUC-0002,PACRI,Alliance Parisienne des Instituts de Recherche en Cancérologie(2011), European Project: 311660,EC:FP7:ERC,ERC-2012-StG_20111109,CEVAL(2013), and European Project: 305421,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EUROFANCOLEN(2013)

Subjects
MDM4, Fanconi anemia, precision medicine, [SDV]Life Sciences [q-bio], Genetics, leukemia, clonal hematopoiesis, Molecular Medicine, Cell Biology, TP53, mutational signature, genomic instability, BRCA2
Abstract

International audience; Fanconi anemia (FA) patients experience chromosome instability, yielding hematopoietic stem/progenitor cell (HSPC) exhaustion and predisposition to poor-prognosis myeloid leukemia. Based on a longitudinal cohort of 335 patients, we performed clinical, genomic, and functional studies in 62 patients with clonal evolution. We found a unique pattern of somatic structural variants and mutations that shares features of BRCA-related cancers, the FA-hallmark being unbalanced, microhomology-mediated translocations driving copy-number alterations. Half the patients developed chromosome 1q gain, driving clonal hematopoiesis through MDM4 trisomy downmodulating p53 signaling later followed by secondary acute myeloid lukemia genomic alterations. Functionally, MDM4 triplication conferred greater fitness to murine and human primary FA HSPCs, rescued inflammation-mediated bone marrow failure, and drove clonal dominance in FA mouse models, while targeting MDM4 impaired leukemia cells in vitro and in vivo. Our results identify a linear route toward secondary leukemogenesis whereby early MDM4-driven downregulation of basal p53 activation plays a pivotal role, opening monitoring and therapeutic prospects.

Published
2023
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2. Germline pathogenic variants in transcription factors predisposing to pediatric acute myeloid leukemia: results from the French ELAM02 trial

Author

Carine Domenech, Marlène Pasquet, Stéphane Ducassou, Arnaud Petit, Paul Saultier, Claude Preudhomme, Nicolas Duployez, Guy Leverger, Hélène Lapillonne, Alice Marceau-Renaut, Laurène Fenwarth, Thierry Leblanc, Pascale Schneider, Virginie Gandemer, Wadih Abou Chahla, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, CHU Bordeaux [Bordeaux], CHU Pontchaillou [Rennes], CHU Toulouse [Toulouse], 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), CHU Rouen, Normandie Université (NU), Hospices Civils de Lyon (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université

Subjects
[SDV]Life Sciences [q-bio], Bioinformatics, Germline, 03 medical and health sciences, 0302 clinical medicine, Text mining, Medicine, Humans, Genetic Predisposition to Disease, Child, Letters to the Editor, Transcription factor, Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, Pediatric acute myeloid leukemia, Hematology, 3. Good health, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, Germ Cells, 030220 oncology & carcinogenesis, Disease Susceptibility, business, Transcription Factors
Abstract

International audience

Published
2021
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3. A circulating subset of BRAFV600E-positive cells in infants with high-risk Langerhans cell histiocytosis treated with BRAF inhibitors

Author

Jean-François Emile, J. Donadieu, Zofia Hélias-Rodzewicz, Geneviève Plat, Nawa Hachem, Sébastien Héritier, Hélène Lapillonne, Rita Poch, Solenne Le Louet, Mohamed-Aziz Barkaoui, François Delhommeau, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], CHU Toulouse [Toulouse], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Conquer Cancer Foundation, CCF, Institut National de la Santé et de la Recherche Médicale, Inserm, Association Histiocytose France, AHF, Association la Petite Maison dans la Prairie, Institut de Veille Sanitaire, InVS, Les 111 des Arts, We would like to thank the patients and their families for their participation in this study. This study was supported by a grant (#11413) from the Conquer Cancer Foundation ASCO Young Investigator Award, funded by the Strike 3 Foundation. This study received grants from the Société Française de lutte contre les Cancers de l’Enfant et de l’Adolescent, the Fédération Enfants et Santé, the Association Recherche et Maladie Hématologiques de l'Enfant, the Association Les 111 des Arts de Paris, and the Association la Petite Maison dans la Prairie. This project received ongoing support from the Association Histiocytose France. The French LCH registry was supported by a grant from InVS and INSERM for the rare‐disease registry. This study was based on research from the Centre de Reference des Histiocytoses ( www.histiocytose.org )., We would like to thank the patients and their families for their participation in this study. This study was supported by a grant (#11413) from the Conquer Cancer Foundation ASCO Young Investigator Award, funded by the Strike 3 Foundation. This study received grants from the Soci?t? Fran?aise de lutte contre les Cancers de l?Enfant et de l?Adolescent, the F?d?ration Enfants et Sant?, the Association Recherche et Maladie H?matologiques de l'Enfant, and the Association la Petite Maison dans la Prairie. This project received ongoing support from the Association Histiocytose France. The French LCH registry was supported by a grant from InVS and INSERM for the rare-disease registry. This study was based on research from the Centre de Reference des Histiocytoses (www.histiocytose.org)., Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and HAL UVSQ, Équipe

Subjects
Myeloid, circulating tumour cells, medicine.medical_treatment, [SDV]Life Sciences [q-bio], medicine.disease_cause, Targeted therapy, BRAF, 03 medical and health sciences, 0302 clinical medicine, Langerhans cell histiocytosis, medicine, Pathological, 030304 developmental biology, 0303 health sciences, Mutation, business.industry, Hematology, Biomarker, Cell sorting, medicine.disease, targeted therapy, 3. Good health, Discontinuation, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Biomarker (medicine), business
Abstract

International audience; BRAF inhibitors are an effective treatment for BRAFV600E-mutated, risk-organ-positive Langerhans cell histiocytosis (RO+ LCH). However, cell-free BRAFV600E DNA often persists during therapy and recurrence frequently occurs after therapy discontinuation. To identify a pathological reservoir of BRAFV600E-mutated cells, we studied peripheral blood cells obtained from six infants with RO+ multisystem (MS) LCH that received targeted therapy. After cell sorting, the BRAFV600E mutation was detected in monocytes (n = 5), B lymphocytes (n = 3), T lymphocytes (n = 2), and myeloid and plasmacytoid dendritic cells (n = 2 each). This biomarker may offer an interesting tool for monitoring the effectiveness of new therapeutic approaches for weaning children with RO+ LCH from targeted therapy.

Published
2021
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4. Human erythroleukemia genetics and transcriptomes identify master transcription factors as functional disease drivers

Author

Silvia Salmoiraghi, Daniel Birnbaum, Loïc Garçon, Frederik Otzen Bagger, Zakia Aid, Alexandre Fagnan, Benjamin Uzan, Stephane de Botton, Maria Riera Piqué-Borràs, Cécile K. Lopez, Christine Dierks, Connor Sweeney, Eric Delabesse, Juerg Schwaller, Elie Robert, Kazuya Shimoda, Zahra Kadri, Thomas Pabst, Jaroslaw P. Maciejewski, Betty Leite, Alexis Caulier, Sébastien Malinge, Samantha Tauchmann, Catherine Carmichael, Amina Kurtovic-Kozaric, Olivier A. Bernard, Virginie Deleuze, Ute M. Moll, Paresh Vyas, Martin Carroll, Veronique De Mas, Orietta Spinelli, Thomas Mercher, Hélène Lapillonne, Cathy Ignacimouttou, Charles G. Mullighan, Eric Soler, V. Gelsi-Boyer, Peter Valent, Cécile Thirant, Jean Baptiste Micol, Eduardo Anguita, Ilaria Iacobucci, Benjamin T. Kile, and Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Myeloid, Erythroblasts, [SDV]Life Sciences [q-bio], Biochemistry, Transcriptome, Mice, 0302 clinical medicine, Mice, Inbred NOD, hemic and lymphatic diseases, Erythropoiesis, GATA1 Transcription Factor, Gene Knock-In Techniques, RNA-Seq, 0303 health sciences, education.field_of_study, Myeloid leukemia, GATA1, Hematology, Middle Aged, Neoplasm Proteins, 3. Good health, DNA-Binding Proteins, Leukemia, Haematopoiesis, Cell Transformation, Neoplastic, medicine.anatomical_structure, Radiation Chimera, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Female, Adult, Immunology, Population, Mice, Transgenic, Biology, Dioxygenases, Genetic Heterogeneity, Young Adult, 03 medical and health sciences, Transcriptional Regulator ERG, Proto-Oncogene Proteins, Exome Sequencing, medicine, Animals, Humans, Epigenetics, education, 030304 developmental biology, Cell Biology, Hematopoietic Stem Cells, medicine.disease, Mice, Inbred C57BL, Repressor Proteins, Mutation, Cancer research, Leukemia, Erythroblastic, Acute, Transcription Factors
Abstract

Acute erythroleukemia (AEL or acute myeloid leukemia [AML]-M6) is a rare but aggressive hematologic malignancy. Previous studies showed that AEL leukemic cells often carry complex karyotypes and mutations in known AML-associated oncogenes. To better define the underlying molecular mechanisms driving the erythroid phenotype, we studied a series of 33 AEL samples representing 3 genetic AEL subgroups including TP53-mutated, epigenetic regulator-mutated (eg, DNMT3A, TET2, or IDH2), and undefined cases with low mutational burden. We established an erythroid vs myeloid transcriptome-based space in which, independently of the molecular subgroup, the majority of the AEL samples exhibited a unique mapping different from both non-M6 AML and myelodysplastic syndrome samples. Notably, >25% of AEL patients, including in the genetically undefined subgroup, showed aberrant expression of key transcriptional regulators, including SKI, ERG, and ETO2. Ectopic expression of these factors in murine erythroid progenitors blocked in vitro erythroid differentiation and led to immortalization associated with decreased chromatin accessibility at GATA1-binding sites and functional interference with GATA1 activity. In vivo models showed development of lethal erythroid, mixed erythroid/myeloid, or other malignancies depending on the cell population in which AEL-associated alterations were expressed. Collectively, our data indicate that AEL is a molecularly heterogeneous disease with an erythroid identity that results in part from the aberrant activity of key erythroid transcription factors in hematopoietic stem or progenitor cells.

Published
2020
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5. Ontogenic changes in hematopoietic hierarchy determine pediatric specificity and disease phenotype in fusion oncogene-driven myeloid leukemia

Author

Cécile K. Lopez, Marie Laure Arcangeli, Eric Delabesse, Sébastien Malinge, Alexandre Fagnan, Isabelle Godin, Franco Locatelli, Françoise Pflumio, Fabien Boudia, Cécile Thirant, Muriel Gaudry, Vaia Stavropoulou, Arnaud Petit, Claus Nerlov, Nathalie Droin, Riccardo Masetti, Paola Ballerini, Zakia Aid, Berthold Göttgens, Olivier Bernard, Sarah Kinston, Erika Brunet, Hélène Lapillonne, Loelia Babin, Juerg Schwaller, Antoine H.F.M. Peters, Elie Robert, Yann Lécluse, Bastien Job, Chrystele Bilhou-Nabera, Jean-Luc Villeval, Camille Lobry, William Vainchenker, Thomas Mercher, Esteve Noguera, M'Boyba Diop, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], 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), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de Bioinformatique [Gustave Roussy], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bases fondamentales et stratégies nouvelles en cancérologie (BFSNC - IFR54), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulation et dynamique des génomes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Santa Lucia Foundation, IRCSS, Rome, University of Oxford [Oxford], Images et Modèles, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Cambridge [UK] (CAM), Service Procédés et Innovations Industriels (SPII), eRcane, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique des tumeurs (U985), Institut Gustave Roussy (IGR)-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)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche et d'Etude en Droit et Science Politique (CREDESPO), Université de Bourgogne (UB), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lopez C.K., Noguera E., Stavropoulou V., Robert E., Aid Z., Ballerini P., Bilhou-Nabera C., Lapillonne H., Boudia F., Thirant C., Fagnan A., Arcangeli M.-L., Kinston S.J., Diop M., Job B., Lecluse Y., Brunet E., Babin L., Villeval J.L., Delabesse E., Peters A.H.F.M., Vainchenker W., Gaudry M., Masetti R., Locatelli F., Malinge S., Nerlov C., Droin N., Lobry C., Godin I., Bernard O.A., Gottgens B., Petit A., Pflumio F., Schwaller J., Mercher T., Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire d'Hématologie [AP-HP Hôpital Armand Trousseau], Cellules Souches et Radiations (SCSR (U967 / UMR-E_008)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Brunet, Erika [0000-0002-1726-4673], Malinge, Sébastien [0000-0002-9533-7778], Droin, Nathalie [0000-0002-6099-5324], Godin, Isabelle [0000-0001-8577-8388], Göttgens, Berthold [0000-0001-6302-5705], Schwaller, Juerg [0000-0001-8616-0096], Mercher, Thomas [0000-0003-1552-087X], Apollo - University of Cambridge Repository, Centre de Psychiatrie et Neurosciences (U894), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Myeloid, Oncogene Proteins, Fusion, Oncogene Proteins, Fusion gene, Mice, 0302 clinical medicine, AML, CEBPA, GENOMIC ALTERATIONS, Tumor Cells, Cultured, TRANSCRIPTION FACTOR, RNA-SEQ, Child, ComputingMilieux_MISCELLANEOUS, GENE-EXPRESSION, Age Factors, Myeloid leukemia, GATA1, 3. Good health, Leukemia, Myeloid, Acute, Leukemia, Haematopoiesis, medicine.anatomical_structure, DIFFERENTIATION, Oncology, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Child, Preschool, 030220 oncology & carcinogenesis, Female, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, children, ACUTE MEGAKARYOBLASTIC LEUKEMIA, transcription factors, medicine, Animals, Humans, FETAL, pediatric acute myeloid leukemia, LINEAGE COMMITMENT, Infant, medicine.disease, STEM-CELL, SELF-RENEWAL, 030104 developmental biology, Cancer research, Neoplasm Transplantation
Abstract

Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as ETO2–GLIS2, are associated with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that ETO2–GLIS2 expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia whereas expression in adult bone marrow hematopoietic stem cells resulted in a shift toward myeloid transformation with a strikingly delayed in vivo leukemogenic potential. Chromatin accessibility and single-cell transcriptome analyses indicate ontogeny-dependent intrinsic and ETO2–GLIS2-induced differences in the activities of key transcription factors, including ERG, SPI1, GATA1, and CEBPA. Importantly, switching off the fusion oncogene restored terminal differentiation of the leukemic blasts. Together, these data show that aggressiveness and phenotypes in pediatric acute myeloid leukemia result from an ontogeny-related differential susceptibility to transformation by fusion oncogenes. Significance: This work demonstrates that the clinical phenotype of pediatric acute myeloid leukemia is determined by ontogeny-dependent susceptibility for transformation by oncogenic fusion genes. The phenotype is maintained by potentially reversible alteration of key transcription factors, indicating that targeting of the fusions may overcome the differentiation blockage and revert the leukemic state. See related commentary by Cruz Hernandez and Vyas, p. 1653. This article is highlighted in the In This Issue feature, p. 1631

Published
2019
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6. Les mutations oncogénétiques associées à la MRD améliorent la prédiction du risque de rechute des leucémies aiguës lymphoblastiques T pédiatriques

Author

Gérard Michel, Jean Soulier, Sandrine Thouvenin, André Baruchel, Judith Landman-Parker, Nathalie Grardel, Paola Ballerini, Sylvie Chevret, Aurore Touzart, Guy Leverger, Elizabeth Macintyre, Claude Preudhomme, Arnaud Petit, Jean-Michel Cayuela, Vahid Asnafi, Amélie Trinquand, Hélène Lapillonne, Claudine Schmitt, Benoit Brethon, Sorbonne Université (SU), Hôpital Necker, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, AP-HP Hôpital universitaire Robert-Debré [Paris], Centre Hospitalier Universitaire de Nancy (CHU Nancy), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Assistance Publique - Hôpitaux de Marseille (APHM)

Subjects
0301 basic medicine, medicine.medical_specialty, Neoplasm, Residual, Adolescent, Lymphoblastic Leukemia, T cell, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Biochemistry, Gastroenterology, Disease-Free Survival, Leukocyte Count, 03 medical and health sciences, 0302 clinical medicine, Recurrence, hemic and lymphatic diseases, White blood cell, Internal medicine, medicine, Humans, PTEN, Cumulative incidence, Child, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, biology, business.industry, Proportional hazards model, Infant, Newborn, Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Oncogenes, Cell Biology, Hematology, Stepwise regression, Prognosis, Minimal residual disease, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, Child, Preschool, 030220 oncology & carcinogenesis, Mutation, biology.protein, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genes, Neoplasm
Abstract

Risk stratification in childhood T-cell acute lymphoblastic leukemia (T-ALL) is mainly based on minimal residual disease (MRD) quantification. Whether oncogenetic mutation profiles can improve the discrimination of MRD-defined risk categories was unknown. Two hundred and twenty FRALLE2000T-treated patients were tested retrospectively for NOTCH1/FBXW7/RAS and PTEN alterations. Patients with NOTCH1/FBXW7 (N/F) mutations and RAS/PTEN (R/P) germ line (GL) were classified as oncogenetic low risk (gLoR; n = 111), whereas those with N/F GL and R/P GL mutations or N/F and R/P mutations were classified as high risk (gHiR; n = 109). Day 35 MRD status was available for 191 patients. Five-year cumulative incidence of relapse (CIR) and disease-free survival were 36% and 60% for gHiR patients and 11% and 89% for gLoR patients, respectively. Importantly, among the 60% of patients with MRD

Published
2018
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7. Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells

Author

Nathalie Chevallier, Loïc Garçon, Laurence Guyonneau-Harmand, Hélène Lapillonne, Luc Douay, Marc Benderitter, Brigitte Birebent, François Delhommeau, Christophe Desterke, Thierry Jaffredo, Bruno Homme, Alain Chapel, Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire d'Hématologie et d'Immunologie [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), EFS Ile de France, Unité d’Ingénierie et de Thérapie Cellulaire, Créteil, F-94017, France., PRP-HOM/SRBE/LRTE, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Unité de service de l'Institut André Lwoff (US 33 Inserm), Hôpital Paul Brousse-Institut André Lwoff [Villejuif] (IAL), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Migration et différenciation des cellules souches hématopoiétiques = Migration and differentiation of hematopoietic stem cells (LBD-E06), Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), 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)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), 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)-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 la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Direction Générale de l’Armement ASTRID/ANR program, Etablissement Français du Sang APR 2013, association 'Combattre La Leucémie', joint grant from Agence Nationale pour la Recherche/California Institute for Regenerative Medicine (ANR/CIRM 0001-02), Laboratoire de Radiopathologie et de Thérapies Expérimentales (IRSN/PRP-HOM/SRBE/LRTE), Unité mixte de service UMS33 [Institut André Lwoff] (UMS33 Inserm/IAL), Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut André Lwoff [Villejuif] (IAL), and Jaffredo, Thierry

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Myeloid, Population, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, CXCR4, 03 medical and health sciences, 0302 clinical medicine, Directed differentiation, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Progenitor cell, education, hemogenic endothelium, 030304 developmental biology, Hemogenic endothelium, 0303 health sciences, education.field_of_study, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Cell biology, hematopoietic stem cells, human induced pluripotent stem cells, Haematopoiesis, hematopoietic reconstitution, medicine.anatomical_structure, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], 030220 oncology & carcinogenesis, Immunology, Homing (hematopoietic)
Abstract

Introductory paragraphThe successful production of Hematopoietic Stem and Progenitor Cells (HSPCs) from human pluripotent sources is conditioned by transgene delivery1-5. We describe here a dedicated and tractable one step, GMP-grade, transgene-free and stroma-free protocol to produce HSPCs from human induced pluripotent stem cells (hiPSCs). This procedure, applied to several sources of hiPSCs with equal efficiency, is based on a directed differentiation with morphogens and cytokines to generate a cell population close to nascent HSPCs or their immediate forerunners i.e., hemogenic endothelial cells6-9. Following engraftment into immunocompromised recipients, this cell population was proved capable of a robust myeloid, lymphoid and definitive red blood cell production in sequential recipients for at least 40 weeks. Further identification of the repopulating cells show that they express the G protein–coupled receptor APELIN (APLNR) and the homing receptor CXCR4. This demonstrates that the generation of bona fide HSPCs from hiPSCs without transgenes is possible and passes through an early endo-hematopoietic intermediate. This work opens the way to the generation of clinical grade HSPCs for the treatment of hematological diseases and holds promise for the analysis of HSPC development in the human species.

Published
2017

8. Unlike ASXL1 and ASXL2 mutations, ASXL3 mutations are rare events in acute myeloid leukemia with t(8;21)

Author

Maxime Bucci, Hélène Lapillonne, Arnaud Petit, Nicolas Duployez, Sandrine Geffroy, Nicolas Boissel, Hervé Dombret, Norbert Ifrah, Aline Renneville, Eric Jourdan, Omar Abdel-Wahab, Claude Preudhomme, Guy Leverger, Jean-Baptiste Micol, Bernardo, Elizabeth, Equipe 3 - Facteurs de persistance des cellules leucémique - (INSERM U837), Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human Oncology and Pathogenesis Program and Leukemia Service [New York, NY, USA], Memorial Sloane Kettering Cancer Center [New York]-Weill Medical College of Cornell University [New York], Hématologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Département d'Hématologie Clinique [CHU d'Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département d'hématologie et d'oncologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM), and Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille]-Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille]

Subjects
0301 basic medicine, Cancer Research, animal structures, Myeloid, Chromosomes, Human, Pair 21, Chromosomal translocation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, medicine.disease_cause, Translocation, Genetic, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Gene expression, medicine, Humans, Epigenetics, Gene, ComputingMilieux_MISCELLANEOUS, Genetics, Mutation, fungi, Myeloid leukemia, Hematology, medicine.disease, Repressor Proteins, Leukemia, Myeloid, Acute, Leukemia, 030104 developmental biology, medicine.anatomical_structure, Oncology, Chromosomes, Human, Pair 8, Transcription Factors
Abstract

Additional sex combs-like (ASXL) genes are human homologues of the Drosophila-Asx gene encoding proteins that control gene expression through the regulation and the recruitment of epigenetic regula...

Published
2016
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9. Molecular signature of erythroblast enucleation in human embryonic stem cells

Author

Nicolas Hebert, Anne-Marie Faussat, Charles Durand, Marie Cambot, Hélène Lapillonne, Shaghayegh Rouzbeh, Christelle Mazurier, Luc Douay, Ladan Kobari, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Transfusion Sanguine [Paris] (INTS), Cancer, Inflammation, Hormones, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie du Développement [IBPS] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-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), CHU Trousseau [APHP], Labex GR-Ex fellowship, Etablissement Francais du Sang (EFS), Fondation pour la recherche medicale, Combattre La Leucemie, DIM Stempole (Paris, France), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), Laboratoire de Biologie du Développement [Paris] (LBD), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), HAL-UPMC, Gestionnaire, and Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID

Subjects
Cell type, Embryonic stem cells, Erythroblasts, Enucleation, Human Embryonic Stem Cells, Embryoid body, Biology, MiR-30a, Erythroblast, hemic and lymphatic diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Humans, Erythropoiesis, RNA, Messenger, Cells, Cultured, Gene knockdown, Cell Differentiation, Cell Biology, Anatomy, Embryonic stem cell, Cell biology, MicroRNAs, Gene Expression Regulation, Molecular Medicine, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Developmental Biology
Abstract

While enucleation is a critical step in the terminal differentiation of human red blood cells, the molecular mechanisms underlying this unique process remain unclear. To investigate erythroblast enucleation, we studied the erythroid differentiation of human embryonic stem cells (hESCs), which provide a unique model for deeper understanding of the development and differentiation of multiple cell types. First, using a two-step protocol, we demonstrated that terminal erythroid differentiation from hESCs is directly dependent on the age of the embryoid bodies. Second, by choosing hESCs in two extreme conditions of erythroid culture, we obtained an original differentiation model which allows one to study the mechanisms underlying the enucleation of erythroid cells by analyzing the gene and miRNA (miR) expression profiles of cells from these two culture conditions. Third, using an integrated analysis of mRNA and miR expression profiles, we identified five miRs potentially involved in erythroblast enucleation. Finally, by selective knockdown of these five miRs we found miR-30a to be a regulator of erythroblast enucleation in hESCs. Stem Cells 2015;33:2431–2441

Published
2015
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10. Proof of principle for transfusion of in vitro-generated red blood cells

Author

Sabine François, Laurent Kiger, Hélène Lapillonne, Germain Trugnan, Hélène Rouard, Séverine Jolly, Thierry Peyrard, Nicolas Hebert, Nathalie Mario, Tiffany Marie, Laurence Harmand, Christelle Mazurier, Marie-Catherine Giarratana, Luc Douay, Jean-Yves Devaux, Agnès Dumont, Pierre-Yves Le Pennec, Innocent Safeukui, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Thérapie Cellulaire [Grenoble], CHU Grenoble-EFS, Immunologie moléculaire des parasites, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Université Pierre et Marie Curie - Paris 6 (UPMC), Trafic Membranaire et Signalisation Dans les Cellules Epitheliales, Institut National de la Transfusion Sanguine [Paris] (INTS), Centre National de Référence pour les Groupes Sanguins (CNRGS), CNRGS, STMicroelectronics [Crolles] (ST-CROLLES), Service de médecine interne [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Différenciation et prolifération des cellules souches adultes. application à la thérapie cellulaire hématopoiétique, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Erythrocytes, Plenary Paper, Antigens, CD34, Mice, SCID, Biochemistry, Blood cell, Hemoglobins, Mice, 0302 clinical medicine, Mice, Inbred NOD, Erythropoiesis, Cells, Cultured, 0303 health sciences, education.field_of_study, Hematology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Transfusion medicine, Cell Differentiation, Erythrocyte Aging, Flow Cytometry, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Blood Group Antigens, Stem cell, Erythrocyte Transfusion, medicine.medical_specialty, Cell Survival, Immunology, Population, Transplantation, Heterologous, Biology, In Vitro Techniques, 03 medical and health sciences, In vivo, Internal medicine, Erythrocyte Deformability, medicine, Animals, Humans, education, 030304 developmental biology, Cell Proliferation, Severe combined immunodeficiency, Cell Biology, medicine.disease, Hematopoietic Stem Cells, Red blood cell
Abstract

In vitro RBC production from stem cells could represent an alternative to classic transfusion products. Until now the clinical feasibility of this concept has not been demonstrated. We addressed the question of the capacity of cultured RBCs (cRBCs) to survive in humans. By using a culture protocol permitting erythroid differentiation from peripheral CD34+ HSC, we generated a homogeneous population of cRBC functional in terms of their deformability, enzyme content, capacity of their hemoglobin to fix/release oxygen, and expression of blood group antigens. We then demonstrated in the nonobese diabetes/severe combined immunodeficiency mouse that cRBC encountered in vivo the conditions necessary for their complete maturation. These data provided the rationale for injecting into one human a homogeneous sample of 1010 cRBCs generated under good manufacturing practice conditions and labeled with 51Cr. The level of these cells in the circulation 26 days after injection was between 41% and 63%, which compares favorably with the reported half-life of 28 ± 2 days for native RBCs. Their survival in vivo testifies globally to their quality and functionality. These data establish the proof of principle for transfusion of in vitro–generated RBCs and path the way toward new developments in transfusion medicine. This study is registered at http://www.clinicaltrials.gov as NCT0929266.

Published
2011
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11. A cytometric study of the red blood cells in gaucher disease reveals their abnormal shape that may be involved in increased erythrophagocytosis

Author

Coralia Cotoraci, Jean Montreuil, Cyril Mignot, Jean-Pierre Tissier, Daniela Bratosin, Thierry Billette de Villemeur, Olivier Hermine, Hélène Lapillonne, National Institute of Research and Development for Biological Sciences (NIRBDS), Vasile Goldiș Western University of Arad, Partenaires INRAE, Processus aux Interfaces et Hygiène des Matériaux (PIHM), Institut National de la Recherche Agronomique (INRA), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lille, Sciences et Technologies, Centre National de la Recherche Scientifique [8576], Romanian Ministry of Education and Research [PN 09 36 - BIODIV], MacoPharma Company, Tourcoing, France, Ministere de l'Enseignement Superieur de la Recherche et de la Technologie, Slama, Catherine, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Université des Sciences et Technologies (Lille 1) (USTL)

Subjects
Male, Pathology, calcein-AM, erythroptosis, [SDV]Life Sciences [q-bio], 0302 clinical medicine, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Child, CD47, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, desialylation, medicine.diagnostic_test, phosphatidylserine exposure, Enzyme replacement therapy, Erythrophagocytosis, erythrophagocytosis, 3. Good health, Cytophagocytosis, Child, Preschool, 030220 oncology & carcinogenesis, Glucosylceramidase, scanning electron microscopy, Senescence, medicine.medical_specialty, Histology, Adolescent, Cell Survival, Anemia, Phagocytosis, Asialoglycoproteins, Erythrocytes, Abnormal, CD47 Antigen, Phosphatidylserines, Biology, Pathology and Forensic Medicine, Flow cytometry, 03 medical and health sciences, medicine, gaucher disease, Humans, Enzyme Replacement Therapy, Sphingolipidosis, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, terms, 030304 developmental biology, flow cytometry, Cell Biology, medicine.disease, Immunology, erythrocytes, Glucocerebrosidase, Biomarkers
Abstract

International audience; Gaucher disease is a sphingolipidosis caused by a deficiency of the enzyme glucocerebrosidase. Macrophages transform into pathogenic Gaucher cells following the phagocytosis of red blood cells (RBCs) and subsequent accumulation of glucosylceramide. Enhanced erythrophagocytosis is one feature of the disease indicating abnormal macrophage-RBC interactions. We hypothesized that the erythrophagocytosis observed in Gaucher disease may be at least partly due to abnormalities in the RBCs themselves. Methods: To investigate this hypothesis, we used flow cytometry FSC/SSC to study RBCs sampled from seven patients with Gaucher disease in terms of their shape and the expression of markers of senescence and phagocytosis. Cells from two of the seven patients were evaluated before and 9 months after the start of enzyme-replacement therapy. Results: Untreated patients were found to have abnormal flow-cytometry profiles suggesting an alteration of Gaucher RBC morphology. Scanning electron microscopy confirmed this finding by revealing many abnormally shaped RBCs. Whereas there was no evidence of desialylation of membrane glycoconjugates or phosphatidylserine exposure, RBC viability (calcein-AM test) and CD47 expression were reduced. These anomalies found in RBCs sampled from two patients before treatment, were no longer present after a 9 month-long enzyme-replacement therapy. Conclusions: We report on previously overlooked alterations of Gaucher RBCs that may facilitate erythrophagocytosis in untreated patients. Their potential role in the anemia, the excess of aggregation and rheological anomalies associated with Gaucher disease must now be addressed. RBC anomalies may take part in the abnormal crosstalk between RBCs and macrophages leading to the accumulation of Gaucher cells. (C) 2010 International Clinical Cytometry Society

Published
2011
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12. Analysis of the cell cycle in mouse embryonic stem cells

Author

Pierre Savatier, Ludmila Jirmanova, Luigi Vitelli, Hélène Lapillonne, Jacques Samarut, Unité mixte de recherche biologie moléculaire de la cellule, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), ProdInra, Migration, and École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Homeobox protein NANOG, 0303 health sciences, Cellular differentiation, Rex1, [SDV]Life Sciences [q-bio], Embryoid body, Biology, Embryonic stem cell, Cell biology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Stem cell, Induced pluripotent stem cell, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Adult stem cell
Abstract

International audience

Published
2002

13. Mortality from malaria in France, 2005 to 2014

Author

Kendjo, Eric, Thellier, Marc, Noël, Harold, Jauréguiberry, Stéphane, Septfons, Alexandra, Mouri, Oussama, Gay, Frédérick, Tantaoui, Ilhame, Caumes, Eric, Houzé, Sandrine, Piarroux, Renaud, Musset, Lise, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Santé publique France Guyane, Santé publique France - French National Public Health Agency [Saint-Maurice, France], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Parasitologie [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), The French imported malaria Study group: C. Strady (CHU Reims), Caroline Lohmann (CH du Moenchsberg, Mulhouse), Celine Arriuberge (CH Trousseau, Paris), Emmanuel Grimprel (CH Trousseau, Paris), Jean-Marie Delarbre (CH du Moenchsberg, Mulhouse), Michel Thibault (CH René Dubos, Pontoise), Mohamadou Niang (CHR Orléans), A. Barrans (CH Sète), A. Martin (CH Périgueux), A. Spiegel (DESP Nord), A. Valentin (CHU Toulouse), A.S. Le Guern (Institut Pasteur, Paris), Adela Angoulvant (CHU Kremlin-Bicêtre, Paris), Adeline Dubois (CH Alès), Adrien Genin (CH Pays d'Aix), Agathe Lebuisson (CHU Cochin), Agnes Riche (CH Angoulême), Agnès Durand (Institut Pasteur, Paris), Agnès Fromont (CH Auxerre), Ahmed Aboubacar (CHU de Strasbourg), Ahmed Fateh Ousser (CH Louis Mourier), Aida Taieb (INTS, Paris), Alain Domergue (CH Alès - Cévennes), Alain Gravet (CH du Moenchsberg, Mulhouse), Alain Lecoustumier (CH de Cahors), Albert Faye (CHU Robert Debré, Paris), Alexander Pfaff (CHU de Strasbourg), Alexandra Faussart (CHU Bichat-Claude Bernard, Paris), Alexandre Chlilek (CHU Nîmes), Alice Borel (CHU Amiens), Alice Pérignon (CHU Pitié-Salpêtrière, Paris), Ana Mendes-Mreira (CH La Rochelle), André Gardrat (CH d’Evreux), Ange Kissila (CH Provins), Angèle LI (CH Creil (Laënnec)), Anne Cady (CH Bretagne Atlantique), Anne Debourgogne (CHU de Nancy), Anne Delaval (CHI Robert Ballanger, Aulnay-sous-Bois), Anne Goepp (CHI Villeneuve St Georges), Anne Marfaing-Koka (Hôpital Antoine-Béclère), Anne Pauline Bellanger (CHU Besançon, Jean Minjoz), Anne Vincenot-Blouin (CH Meaux), Anne-Marie Teychene-Coutet (CH Bondy-Jean Verdier), Anne-Sophie Deleplancque (CH Lille), Annick Verhaeghe (CH de Dunkerque), Annie Motard-Picheloup (CHI Fréjus St Raphaël), Antoine Berry (CHU Toulouse), Antoine Huguenin (CHU Reims), Arnaud Bouvet (CH Bretagne Atlantique), Audrey Merens (HIA Begin), Aurelie Roide (CHU Lariboisière, Paris), Aurore Sanson (CH Jacques Cœur, Bourges), Aurélie Fricot (CHU Necker), Aurélie Guigon (CHR Orléans), Benfatallah Dhouha (CHU Necker, Paris), Benjamin Wyplosz (CHU Kremlin-Bicêtre, Paris), Benoît Henri (INTS, Paris), Bernadette Buret (CH Niort), Bernadette Cuisenier (CHU Dijon), Bernadette Worms (CHU Dijon), Bernard Faugère (CH Timone, Marseille), Biligui Sylvestre (CHU Pitié-Salpêtrière, Paris), Boualem Sendid (CH Lille), Bruno Megarbane (CHU Lariboisière, Paris), Bruno Pradines (Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, France, Aix Marseille University, IRD, SSA, AP-HM, VITROME, 13005 Marseille, France, IHU Méditerranée Infection, 13005 Marseille, France, Centre National de Référence du Paludisme, Institut de Recherche Biomédicale des Armées, 13005 Marseille, France), Béatrice Quinet (CH Trousseau, Paris), C. Braidy (CH du Sud Seine et Marne), C. Farrugia (CH de Dourdan), C. Finot (CH de Dreux), Camille Roussel (INTS, Paris), Camille Runel-Belliard (CHU de Bordeaux), Caren Brump (CHU Lariboisière, Paris), Carine Dokoula (CH Jacques Cœur, Bourges), Carmina Camal (CH Louis Mourier), Carole Mackosso (CHU Bichat-Claude Bernard, Paris), Carole Poupon (CH de Gonesse), Caroline Garandeau (CH Angoulême), Catherine Benoit (CH du Sud Seine et Marne), Catherine Branger (CH Louis Mourier), Catherine Brehant (CH La Rochelle), Catherine Desideri-Vaillant (HIA Clermont Tonnerre, Brest), Catherine Kauffmann Lacroix (CH Poitiers), Catherine Lafaurie (CH d’Epernay), Cecile Hombrouck-Alet (CH Blois), Cecile Ramade (Lyon-Croix-Rousse), Celine Damiani (CHU Amiens), Celine Gourmel (CHU Lariboisière, Paris), Chantal Duhamel (CHU Côte de Nacre), Chantal Garabedian (CH Pays d'Aix), Chralotte Chambrion (INTS, Paris), Christelle Morelle (CHU Montpellier), Christelle Pomares Estran (CH Universitaire de Nice), Christelle Prince (CH de Cayenne Andrée Rosemon), Christian Durand (CH Provins), Christian Fulleda (CHU Lariboisière, Paris), Christian Raccurt (CHU Amiens), Christine Chaigneau (GHPSO, Creil), Christine Chemla (CHRU de Reims), Christine Van batten (CH Laënnec, Creil), Christophe Martinaud (HIA Percy, Clamart), Christophe Rapp (HIA Begin), Claire Augé (CHU Bichat-Claude Bernard, Paris), Claire Malbrunot (CH Corbeil Essonne), Claudine Febvre (CH de Montbéliard), Claudine Sarfati (Hôpital Saint-Louis, Paris), Coralie l'Ollivier (CH de la Timone, Marseille), Corinne Huet (Hôpital Louis-Pasteur, Cherbourg-Octeville), Cournac Jean-Marie (HIA Percy, Clamart), Cynthia Pianetti (CH Gabriel Martin, La Réunion), Cécile Angebault (CHU Necker, Paris), Cécile Ficko (HIA Begin), Cécile Garnaud (CHU de Grenoble), Cécile Leprince (CHI Robert Ballanger, Aulnay-sous-Bois), Céliat Merat (CHU Nantes), Céline Dard (CHU de Grenoble), Céline Nourrisson (CHRU Clermont-Ferrand), Céline Tournus (Hôpital Delafontaine, Saint-Denis), Daniel Azjenberg (CHU Dupuytren, Limoges), Daniel Camus (CH Lille), Daniel Lusina (CHI Robert Ballanger, Aulnay-sous-Bois), Daniel Parzy (IMTSSA, Marseille), Denis Pons (CHRU Clermont-Ferrand), Denis Filisetti (CHU Strasbourg), Denis Malvy (CHU de Bordeaux), Didier Basset (CHU Montpellier), Didier Jan (CH Laval), Didier Poisson (CHR Orléans), Didier Raffenot (CH Chambéry), Dieudonné Bemba (CH Bondy-Jean Verdier), Dominique Maubon (CHU de Grenoble), Dominique Mazier (CHU Pitié-Salpêtrière, Paris), Dominique Popjora (CH Trousseau, Paris), Dominique Toubas (CHRU de Reims), Dorothée Quino (CHRU Morvan, Brest), Alioune Ndour (INTS, Paris), Ducout Louis (CH de la Côte Basque), Duong Thanh Hai (CHRU Bretonneau), E. Boyer (CH Le Mans), Edgar Ombandza (CH Provins), Edith Mazars (CH de Valenciennes), Elisabeth Buffet (CH de Epernay), Elodie Collin (CHI Robert Ballanger, Aulnay-sous-Bois), Elodie Meynet (CH Annecy Genevois), Emeline Scherer (CHU Besançon, Jean Minjoz), Emilie Fréalle (CH Lille), Emilie Klein (CHU Lariboisière, Paris), Emilie Sitterle (CHU Necker, Paris), Emily Ronez (CHU Lariboisière, Paris), Emmanuel Dutoit (CH Lille), Enrique Casalino (CHU Bichat-Claude Bernard, Paris), Eric Caumes (CHU Pitié-Salpêtrière, Paris), Eric Dannaoui (Hôpital Européen Georges Pompidou, Paris), Eric Gardien (CH de Draguignan, Bordeaux), Eric Kendjo (CHU Pitié-Salpêtrière, Paris),Eric d'Ortenzio (CHU Bichat-Claude Bernard, Paris), Ermanno Candolfi (CHU de Strasbourg), Estelle Perraud-Cateau (CH Poitiers), Eterne Twizeyimana (CH du Cotentin), F. Roblot (CH Poitiers), Fabienne Pateyron (CH Provins), Fabrice Bruneel (CH de Versailles, André Mignot), Fabrice Legros (CNR du paludisme), Fabrice Simon (HIA Laveran), Fakhri Jeddi (CHU Nantes), Farida M. Benaoudia (CH Troyes), Faïzi Ajana (CH Tourcoing), Felix Djossou (CH de Cayenne Andrée Rosemon), Firouze Banisadr (CHRU de Reims), Florent Morio (CHU Nantes), Francis Derouin (Hôpital Saint-Louis, Paris), Francois Moussel (CH François-Quesnay, Mantes-La-Jolie), Francoise Foulet (CHU Henri Mondor), François Peyron (Lyon-Croix-Rousse), Françoise Benoit-Vical (CHU Toulouse), Françoise Botterel (CHU Henri Mondor), Françoise Gayandrieu (CHU Nantes), Françoise Schmitt (CH du Moenchsberg, Mulhouse), Frederic Ariey (CHU Cochin, Paris), Frédéric Grenouillet (CHU Jean Minjoz, Besançon), Frédéric Sorge (CHU Necker), Frédérique Gay (CHU Pitié-Salpêtrière, Paris), Frédérique Foudrinier (CHRU de Reims), G. Courrouble (CH Blois), G. Gallou (CH de Falaise), G. Julienne (CH Belfort), G. Philippon (Centre Médical CMETE, Paris), Gauthier Pean-de-Ponfilly (CHU Lariboisière, Paris), Geneviève Grise (CH d’Elbeuf), Ghania Belkacem Belkadi (CH Tenon), Gilbert Lorre (CHD La Roche-sur-Yon), Gilles Gargala (CHU Rouen), Gilles Nevez (CHRU Morvan, Brest), Gisele Dewulf (CH de Valenciennes), Guillaume Désoubeaux (CHRU Bretonneau, Tours), Guillaume Escriou (CHU Bichat-Claude Bernard, Paris), Guillaume Le Loup (CH Tenon, Paris), Guillaume Menard (HIA Saint-Anne, Toulon), Guy Carroger (CH Jacques Cœur, Bourges), Guy Galeazzi (CH Louis Mourier), Gwénaël le Moal (CH Poitiers), Hana Talabani (CHU Cochin, Paris), Hanene Abid (CHU Necker, Paris), Helene Broutier (CHI Robert Ballanger, Aulnay-sous-Bois), Herve Pelloux (CHU de Grenoble), Houria Ichou (CH Louis Mourier), Hugo Laurent (CHU Lariboisière, Paris), Hélène Broutier (CH Meaux), Hélène Lapillonne (CH Trousseau, Paris), Hélène Yera (CHU Cochin, Paris), Hélène savini (HIA Laveran), I. Hermes (CH Saint-Malo), Ilhame Tantaoui (CHU Pitié-Salpêtrière, Paris), Isabelle Poilane (CH Bondy-Jean Verdier), Isabelle Amouroux (Hôpital Antoine-Béclère), Isabelle Mazurier (Hôpitaux Civils de Colmar), Isabelle Salimbeni (CH de Cannes), Isabelle Tawa (Centre Médical CMETE, Paris), J Cuziat (CH Saint-Nazaire), J. Bernard Poux (CH de Val d'Ariège - Foix), J. Heurtet (CH Beauvais), J. Rome (CH de Fougères), J. Truchot (CHU Lariboisière, Paris), J.M. Segalin (CHR Orleans), Jacques Gaillat (CH Annecy Genevois), Jacques Le bras (CHU Bichat-Claude Bernard, Paris), Jacques Thevenot (Centre Médical CMETE, Paris), Jacques Vaucel (CH Saint-Brieuc), Jean Dunand (Hôpital Ambroise Paré), Jean Benjamin Murat (CH de Roanne), Jean Marie Trapateau (CH Angoulême), Jean Yves Peltier (CHI Poissy-st-germain), Jean-Etienne Pilo (HIA Begin), Jean-Francois Magnaval (CHU Toulouse), Jean-François Faucher (CHU Jean Minjoz, Limoge), Jean-Paul Boutin (DESP Sud), Jean-Paul Couaillac (CH de Cahors), Jean-Philippe Breux (CH Cholet), Jean-Pierre Hurst (CH Jacques Monod, Le Havre), Jean-Yves Siriez (CHU Robert Debré, Paris), Jean-philippe Bouchara (CHU Angers), Jerome Clain (CHU Bichat-Claude Bernard, Paris), Jerome Naudin (CHU Robert Debré, Paris), Jordan Leroy (CH Lille), Josette Jehan (CH du Cotentin), Joudia Najid (CHU Pitié-Salpêtrière, Paris), Judith Gorlicki (CHU Lariboisière, Paris), Julie Bonhomme (CHU Côte de Nacre), Julie Brunet (CHU de Strasbourg), Jérome Guinard (CHR Orleans), Karima Cheikh (CHU Henri Mondor), L. Pougnet (HIA Clermont Tonnerre, Brest), Lauren Pull (CHU Robert Debré, Paris), Laurence Millon (CHU Jean Minjoz, Besançon), Laurence Campergue-Mayer (CH Avignon), Laurence Estepa (CH Blois), Laurence Lachaud (CHU Nîmes), Laurent Aaron (CH Jacques Cœur, Bourges), Laurent Bret (CHR Orléans), Laurent Guillaume (CH Blois), Liliane Ciceron (CHU Pitié-Salpêtrière, Paris), Lionnel Bertaux (CNR du paludisme), Lise Musset (Institut Pasteur, Guyane), Louise Basmacyan (CHU Dijon), Loïc Favennec (CHU Rouen), Luce Landraud (CH Louis Mourier), Lucile Cadot (CH Alès - Cévennes), Ludovic de Gentile (CHU Angers), Luis Macias (CHU Bichat-Claude Bernard, Paris), Luu-ly Pham (CHU Kremlin-Bicêtre, Paris), M. Cambon (CHRU Clermont-Ferrand), M.F. Biava (CHU de Nancy), M.H. Kiefer (CH du Moenchsberg), M.P. Carlotti (CNR du paludisme), Madeleine Fontrouge (CH de Gonesse), Marc Pihet (CHU Angers), Marc Thellier (CHU Pitié-Salpêtrière, Paris), Marie-Catherine Receveur (CHU de Bordeaux), Marie-Claire Machouart (CHU de Nancy), Marie-Elisabeth Bougnoux (CHU Necker, Paris), Marie-Laure Bigel (CH François-Quesnay, Mantes-la-Jolie), Marie-Laure Darde (CHU Dupuyrien, Limoges), Marie-Nadège Bachelier (CH Jacques Cœur, Bourges), Marion Almeras (CH Béziers), Marion Leterrier (CHU Nantes), Marion Leterrier (CHD La Roche-sur-Yon), Martin Danis (CHU Pitié-Salpêtrière, Paris), Martin G (CH du Cotentin), Martine Bloch (CH Louis Mourier), Martine Liance (CHU Henri Mondor, Paris), Marylin Madamet (IMTSSA, Marseille), Matthieu Revest (CHU Pontchaillou, Rennes),Matthieu Mechain (CHU de Bordeaux), Maxime Thouvenin (CH Troyes), Mermond Sylvain (Institut Pasteur, Nouméa), Michel Develoux (CH Tenon, Paris), Michel Miegeville (CHU Nantes), Milène Sasso (CHU Nîmes), Mohamed Diaby (CH Vernon), Monique Marty (CH La Rochelle), Monique Greze (CH Albi), Monique Lemoine (CHU Bichat-Claude Bernard, Paris), Mouri Oussama (CHU Pitié-Salpêtrière, Paris), Muriel Cornet (Hôpital Hôtel-Dieu, Paris), Muriel Mimoun Ayache (CH Trousseau), Muriel Nicolas (CHU Pointe-à-Pitre / Abymes), Muriel Roumier (CH Arles), Muriel Silva (CH Jacques Monod), Mylène Penot (CERBA), Myriam Gharbi (CHU Bichat-Claude Bernard, Paris), Nadia Guennouni (CHU Bichat-Claude Bernard, Paris), Nadine Godineau (Hôpital Delafontaine, Saint-Denis), Naima Dahane (CHU Cochin, Paris), Nathalie Bourgeois (CHU Montpellier), Nathalie Desuremain (CH Trousseau, Paris), Nathalie Fauchet (CHI de Créteil), Nathalie Parez (CH Louis Mourier), Nathalie Wilhelm (CH de Cahors), Nawel Ait-Ammar (Hôpital Ambroise Paré), Nayla Nassar (CH Auxerre), Nicolas Argy (CHU Bichat-Claude Bernard, Paris), Nicolas Blondiaux (CH Tourcoing), Nicolas Taudon (CERBA), Nicole Desbois-Nogard (CHU de la Martinique), Noura Hassouni (CHU Necker), Odile Bouret-Dubouis (CH Bretagne Atlantique), Odile Eloy (CH de Versailles, André Mignot), Odile Falguiere (CH Béziers), Odile Fenneteau (CHU Robert Debré, Paris), Olivia Bandin (Hôpital Saint-Camille/Bry-sur-Marne), Olivier Albert (CHU de Bordeaux), Olivier Bouchaud (CH Bobigny-Avicenne), Olivier Patey (CHI Villeneuve St. Georges), Olivier Rogeaux (CH Chambéry), P. Clergeau (CH Sallanches), P. Daumain (CH de Dourdan), P.H. Consigny (Institut Pasteur, Paris), Paméla Chauvin (CHU Toulouse), Pascal Delaunay (CH Universitaire de Nice), Pascal Hazera (CH Saint-Lo), Pascal Houze (Hôpital Saint Louis, Paris), Pascal Millet (CHU de Bordeaux), Pascal Pouedras (CH Bretagne Atlantique), Pascale Penn (CH Le Mans), Patrice Agnamey (CHU Amiens), Patrice Bourrée (CHU Kremlin-Bicêtre, Paris), Patricia Barbut (CH Longjumeau), Patricia Brugel (CH Antibes Juan-Les-Pins), Patricia Roux (CH Saint-Antoine, Paris), Patrick Leguen (HIA Clermont Tonnerre, Brest), Patrick Valayer (CH Notre-Dame de la Miséricorde), Pauline Caraux-Paz (CHI Villeneuve St Georges), Pauline Touroultjupin (CH Cholet), Philippe Abboud (CHU Rouen), Philippe Cormier (CH d’Evry), Philippe Minodier (CH Marseille Nord), Philippe Moskovtchenko (Hôpitaux Civils de Colmar), Philippe Parola (CH Marseille Nord), Philippe Poirier (CHRU Clermont-Ferrand), Philippe Stolidi (CH Aubagne), Pierre Patoz (CH Tourcoing), Pierre Buffet (INTS, Paris), Pierre Buffet (CHU Pitié-Salpêtrière, Paris), Pierre Flori (CH Saint-Etienne), Pierre Marty (CH Universitaire de Nice), Pierre Mornand (CH Trousseau, Paris), Pinel Claudine (CHU de Grenoble), R. Dahan (CHU de Strasbourg), R. Devallière (CH Saint-Nazaire), R. Mazataud (CH Vitry le François), Rahaf Haj Hamid (CH Louis Mourier), Regis Courtin (CHU Pitié-Salpêtrière, Paris), Renaud Blonde (CHU Robert Debré, Paris), René Nabias (CHI Poissy-st-germain), Roland Fabre (HIA Begin), Rose-Anne Lavergne (CHU Nantes), Roxane Courtois (CH Cholet), Rym Chouk Turki (CHU Henri Mondor), Rémy Durand (CH Bobigny-Avicenne), Réné Nabias (CHU Necker, Paris), Sabah Kubab (CH Corbeil Essonne), Sabine Lasserre (CH Trousseau, Paris), Samia Hamane (Hôpital Saint-Louis, Paris), Sandrine Cojean (CHU Bichat-Claude Bernard, Paris), Sandrine Houze (CHU Bichat-Claude Bernard, Paris), Sophie Matheron (CHU Bichat-Claude Bernard, Paris), Sorya Belaz (CHU Pontchaillou, Rennes), Stephane Jaureguiberry (CHU Pitié-Salpêtrière, Paris), Stephane Ranque (CH de la Timone, Marseille), Stephanie Dulucq (CHU de Bordeaux), Stéphane Bretagne (Hôpital Saint-Louis, Paris), Stéphane Pelleau (Institut Pasteur, Guyane), Stéphane Picot (Hospices Civils de Lyon), Sylvain Clauser (Hôpital Ambroise Paré), Sylviane Chevrier (CHU Pontchaillou, Rennes), Sylviane Dydymski (CHRU Clermont-Ferrand), Sylvie Lariven (CHU Bichat-Claude Bernard, Paris), Sylvie Lhopital (CH Vernon), Sylvie Maurellet Evrard (CHI Villeneuve St Georges), Sylvie Roulaud (CH Angouleme), Sébastien Larréché (HIA Begin), Thi-Hai-Chau Trinh (CHR Orléans), Thierry Ancelle (CHU Cochin, Paris), Thierry Pistone (CHU de Bordeaux), Thomas Hanslik (Hôpital Ambroise Paré), Thomas Guimard (CHD La Roche-sur-Yon), Timothée Klopfenstein (CHU Besançon, Jean Minjoz), Valerie Fuster-Dumas (CHU de Bordeaux), Veronique Blanc-Amrane (CH Antibes Juan-Les-Pins), Veronique Delcey (CHU Lariboisière, Paris), Veronique Sarrasin-Hubert (CHU Bichat-Claude Bernard, Paris), Vincent Foissaud (HIA Percy, Clamart), Virginie Mouton-Rioux (CH Bretagne Atlantique), Virginie Vitrat (CH Annecy Genevois), Véronique Jan-Lasserre (CH Lagny-sur-Marne), Xavier Nicolas (HIA Clermont Tonnerre, Brest), Y. Costa (CH Lagny-sur-Marne), Yassamine Lazrek (Institut Pasteur, Guyane), Yaye Senghor (Hôpital Saint Joseph, Paris), Yohann Le Govic (CHU Angers), Yves Guimard (CH Jacques Cœur, Bourges), Yves Poinsignon (CH Bretagne Atlantique), Claude flamand (Institut Pasteur, Guyane), C.N. guyen (CH Trousseau, Paris), G. Noël (CH Marseille Nord), G. Soula (CH Marseille Nord), J.M.Didier (CH Vesoul), M.F. Raynaud (CH Antibes Juan-Les-Pins), M. Julien (CH Béziers), M. Morillon (HIA Laveran), M.P. Carlotti (IMTSSA), P. Chantelat (CH Vesoul), P. Dussert (CH Belfort), P. Ralaimazava (CH Bobigny-Avicenne), S. Zaouche (CHU Necker, Paris), Élodie Lesteven (CHU Lariboisière, Paris)., Musset, Lise, Centre National de Référence du Paludisme [CHU Pitié-Salpétrière] (CNRpalu), 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
Plasmodium, Epidemiology, FNRCm, MESH: Hospitalization, Mark and recapture, 0302 clinical medicine, MESH: Aged, 80 and over, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, 030212 general & internal medicine, MESH: Incidence, MESH: Travel, Imported malaria, media_common, MESH: Aged, MESH: Middle Aged, MESH: Infant, 3. Good health, MESH: Young Adult, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, surveillance, France, Sex ratio, MESH: Medical Record Linkage, MESH: Disease Notification, 030231 tropical medicine, Notifiable disease, MESH: Malaria, capture-recapture, malaria, MESH: Population Surveillance, 03 medical and health sciences, MESH: Cross-Sectional Studies, Virology, parasitic diseases, medicine, media_common.cataloged_instance, European union, MESH: Communicable Diseases, Imported, MESH: Adolescent, MESH: Hospitals, University, MESH: Humans, business.industry, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, MESH: Adult, medicine.disease, Confidence interval, MESH: Male, Metropolitan France, MESH: France, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, travellers, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Malaria, Demography
Abstract

Introduction Malaria is a notifiable disease in all European Union and European Economic Area countries except Belgium and France, where only autochthonous malaria is notifiable. Although morbidity caused by malaria has been assessed, little is known about mortality incidence. Objective Our aim was to estimate the number of imported malaria-related deaths in hospital in metropolitan France. Methods We matched individual deaths reported between 1 January 2005 and 31 December 2014 to the French National Reference Centre for malaria (FNRCm) with malaria-related deaths from two other sources: the French National Registry on medical causes of death and the French national hospital discharge database. A capture–recapture method with log-linear modelling was used. Age, sex and place of death stratification were applied to remove heterogeneity. Results The estimated malaria-related deaths in metropolitan France during the study period were 205 (95% confidence interval (CI): 191–219). The annual mean number of malaria-related deaths was estimated at 21 (95% CI: 19–22). The FNRCm malaria-related deaths surveillance had a 38% sensitivity (95% CI: 32–44). Among 161 in-hospital individual malaria-related deaths reported from three data sources, the sex ratio (male to female) was 2.6. Median age of the patients was 57 years, ranging from 1 to 89 years. Conclusion The pertinent finding of this report is that malaria-related death records were significantly less* complete than case records. Therefore, data comparison of imported malaria morbidity and mortality between countries should imperatively be assessed using standard indicators weighted according to the completeness of health surveillance systems.

Published
2020
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