Genetic hierarchy and temporal variegation in the clonal history of acute myeloid leukaemia
| Autor: | Hannah Moatti, François Delhommeau, Rémi Favier, Mohamad Mohty, Chrystele Bilhou-Nabera, Fawzia Louache, Virginie Joulin, Ruoping Tang, Aline Betems, Elodie Pronier, Florence Lorre, Pascale Flandrin, Ollivier Legrand, Fanny Fava, Christophe Marzac, Pierre Hirsch, Frédéric Féger, Hélène Boutroux, Hayat Mokrani, Luc Douay, Dominique Bories, Yanyan Zhang |
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| Přispěvatelé: | Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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), MYPAC, Université Pierre et Marie Curie - Paris 6 (UPMC), 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), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), CHU Saint-Antoine [AP-HP], Hématologie moléculaire [CHU Mondor], CHU Henri Mondor, Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], CHU Henri Mondor [Créteil] |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Time Factors Myeloid Science Clone (cell biology) General Physics and Astronomy Biology medicine.disease_cause Somatic evolution in cancer Article General Biochemistry Genetics and Molecular Biology Epigenesis Genetic Clonal Evolution Mice 03 medical and health sciences hemic and lymphatic diseases medicine Animals Humans neoplasms Variegation Gene Rearrangement [SDV.GEN]Life Sciences [q-bio]/Genetics Mutation Multidisciplinary Base Sequence General Chemistry Gene rearrangement medicine.disease Clone Cells Hematopoiesis Leukemia Myeloid Acute Leukemia Haematopoiesis 030104 developmental biology medicine.anatomical_structure Immunology Single-Cell Analysis |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2016, pp.12475. ⟨10.1038/ncomms12475⟩ Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016) Nature Communications, 2016, 7, pp.12475. ⟨10.1038/ncomms12475⟩ |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms12475 |
| Popis: | In acute myeloid leukaemia (AML) initiating pre-leukaemic lesions can be identified through three major hallmarks: their early occurrence in the clone, their persistence at relapse and their ability to initiate multilineage haematopoietic repopulation and leukaemia in vivo. Here we analyse the clonal composition of a series of AML through these characteristics. We find that not only DNMT3A mutations, but also TET2, ASXL1 mutations, core-binding factor and MLL translocations, as well as del(20q) mostly fulfil these criteria. When not eradicated by AML treatments, pre-leukaemic cells with these lesions can re-initiate the leukaemic process at various stages until relapse, with a time-dependent increase in clonal variegation. Based on the nature, order and association of lesions, we delineate recurrent genetic hierarchies of AML. Our data indicate that first lesions, variegation and treatment selection pressure govern the expansion and adaptive behaviour of the malignant clone, shaping AML in a time-dependent manner. Pre-leukaemic clones, together with the propensity to cause disease in mice, are characterized by appearing early in myeloid leukaemia and being found at relapse. Here, the authors identify clones in human samples and find that they are characterized by hierarchically organized genetic lesions, which can be used to track evolution of the disease. |
| Databáze: | OpenAIRE |
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