IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12475.html
   My bibliography  Save this article

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

Author

Listed:
  • Pierre Hirsch

    (Sorbonne Universités, UPMC Univ Paris 06
    INSERM, UMR_S 938
    Sorbonne Universités, UPMC Univ Paris 06, GRC n°7, Groupe de Recherche Clinique sur les Myéloproliférations Aiguës et Chroniques MYPAC
    AP-HP, Hôpital St Antoine, Service d'Hématologie clinique et de thérapie cellulaire)

  • Yanyan Zhang

    (Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 1170
    Institut Gustave Roussy, Univ Paris-Sud, Université Paris Saclay)

  • 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
    Institut Gustave Roussy, Univ Paris-Sud, Université Paris Saclay)

  • Hélène Boutroux

    (Sorbonne Universités, UPMC Univ Paris 06
    INSERM, UMR_S 938
    Sorbonne Universités, UPMC Univ Paris 06, GRC n°7, Groupe de Recherche Clinique sur les Myéloproliférations Aiguës et Chroniques MYPAC
    AP-HP, Hôpital Armand-Trousseau)

  • Elodie Pronier

    (Institut Gustave Roussy, Univ Paris-Sud, Université Paris Saclay)

  • Hannah Moatti

    (Sorbonne Universités, UPMC Univ Paris 06
    INSERM, UMR_S 938
    Sorbonne Universités, UPMC Univ Paris 06, GRC n°7, Groupe de Recherche Clinique sur les Myéloproliférations Aiguës et Chroniques MYPAC)

  • Pascale Flandrin

    (Sorbonne Universités, UPMC Univ Paris 06
    INSERM, UMR_S 938
    Sorbonne Universités, UPMC Univ Paris 06, GRC n°7, Groupe de Recherche Clinique sur les Myéloproliférations Aiguës et Chroniques MYPAC)

  • 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
    Sorbonne Universités, UPMC Univ Paris 06, GRC n°7, Groupe de Recherche Clinique sur les Myéloproliférations Aiguës et Chroniques MYPAC)

  • Luc Douay

    (Sorbonne Universités, UPMC Univ Paris 06
    INSERM, UMR_S 938
    AP-HP, Hôpital Saint-Antoine & Hôpital Armand-Trousseau, Service d’hématologie biologique)

  • Ollivier Legrand

    (Sorbonne Universités, UPMC Univ Paris 06
    INSERM, UMR_S 938
    Sorbonne Universités, UPMC Univ Paris 06, GRC n°7, Groupe de Recherche Clinique sur les Myéloproliférations Aiguës et Chroniques MYPAC
    AP-HP, Hôpital St Antoine, Service d'Hématologie clinique et de thérapie cellulaire)

  • Chrystèle Bilhou-Nabera

    (Sorbonne Universités, UPMC Univ Paris 06
    INSERM, UMR_S 938
    Sorbonne Universités, UPMC Univ Paris 06, GRC n°7, Groupe de Recherche Clinique sur les Myéloproliférations Aiguës et Chroniques MYPAC
    AP-HP, Hôpital Saint-Antoine & Hôpital Armand-Trousseau, Service d’hématologie biologique)

  • Fawzia Louache

    (Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 1170
    Institut Gustave Roussy, Univ Paris-Sud, Université Paris Saclay)

  • François Delhommeau

    (Sorbonne Universités, UPMC Univ Paris 06
    INSERM, UMR_S 938
    Sorbonne Universités, UPMC Univ Paris 06, GRC n°7, Groupe de Recherche Clinique sur les Myéloproliférations Aiguës et Chroniques MYPAC
    AP-HP, Hôpital Saint-Antoine & Hôpital Armand-Trousseau, Service d’hématologie biologique)

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.

Suggested Citation

  • Pierre Hirsch & Yanyan Zhang & Ruoping Tang & Virginie Joulin & Hélène Boutroux & Elodie Pronier & Hannah Moatti & Pascale Flandrin & Christophe Marzac & Dominique Bories & Fanny Fava & Hayat Mokrani , 2016. "Genetic hierarchy and temporal variegation in the clonal history of acute myeloid leukaemia," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12475
    DOI: 10.1038/ncomms12475
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12475
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12475?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12475. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.