Genetic hierarchy and temporal variegation in the clonal history of acute myeloid leukaemia

Pierre Hirsch, Yanyan Zhang, Ruoping Tang, Virginie Joulin, Hélène Boutroux, Elodie Pronier, Hannah Moatti, Pascale Flandrin, Christophe Marzac, Dominique Bories, Fanny Fava, Hayat Mokrani, Aline Betems, Florence Lorre, Rémi Favier, Frédéric Féger, Mohamad Mohty, Luc Douay, Ollivier Legrand, Chrystèle Bilhou-Nabera, Fawzia Louache and François Delhommeau ()
Additional contact information
Pierre Hirsch: Sorbonne Universités, UPMC Univ Paris 06
Yanyan Zhang: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 1170
Ruoping Tang: AP-HP, Hôpital St Antoine, Service d'Hématologie clinique et de thérapie cellulaire
Virginie Joulin: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 1170
Hélène Boutroux: Sorbonne Universités, UPMC Univ Paris 06
Elodie Pronier: Institut Gustave Roussy, Univ Paris-Sud, Université Paris Saclay
Hannah Moatti: Sorbonne Universités, UPMC Univ Paris 06
Pascale Flandrin: Sorbonne Universités, UPMC Univ Paris 06
Christophe Marzac: AP-HP, Hôpital Saint-Antoine & Hôpital Armand-Trousseau, Service d’hématologie biologique
Dominique Bories: AP-HP, Hôpital Henri Mondor, Unité d'Hématologie Moléculaire
Fanny Fava: Sorbonne Universités, UPMC Univ Paris 06
Hayat Mokrani: Institut Gustave Roussy, Univ Paris-Sud, Université Paris Saclay
Aline Betems: Institut Gustave Roussy, Univ Paris-Sud, Université Paris Saclay
Florence Lorre: AP-HP, Hôpital Saint-Antoine, Laboratoire commun de biologie et génétique moléculaires
Rémi Favier: AP-HP, Hôpital Saint-Antoine & Hôpital Armand-Trousseau, Service d’hématologie biologique
Frédéric Féger: AP-HP, Hôpital Saint-Antoine & Hôpital Armand-Trousseau, Service d’hématologie biologique
Mohamad Mohty: Sorbonne Universités, UPMC Univ Paris 06
Luc Douay: Sorbonne Universités, UPMC Univ Paris 06
Ollivier Legrand: Sorbonne Universités, UPMC Univ Paris 06
Chrystèle Bilhou-Nabera: Sorbonne Universités, UPMC Univ Paris 06
Fawzia Louache: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 1170
François Delhommeau: Sorbonne Universités, UPMC Univ Paris 06

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12475

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DOI: 10.1038/ncomms12475

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