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    The origins of acute myeloid leukemia: genetic predispositions and age-related clonal hematopoiesis

    Webinaire de l'Institut Cochin

    Jeudi 15 avril 2021 - 12h00 - Pour obtenir le lien d'accès Zoom, envoyez un mail à

     


    François Delhommeau

    Equipe "Développement hématopoïétique et leucémie: maladies et thérapie cellulaire" - Centre de Recherche Saint-Antoine, Paris, France

     

     invité par Romain Fontaine


     

    Résumé

    Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous group of blood cancers.  Our understanding of the origins of AML results from recent studies that addressed their clonal hierarchy and the biology of normal and malignant hematopoietic stem cells. Several conditions such as aging or genetic diseases predispose to pre-leukemic states that can evolve to distinct types of AML. Our group studies the genetic events that lead to the initiation of pre-leukemic clones, and then to AML. In the context of genetic diseases with increased risk of AML, we are focused on the early emergence of mutant clones in congenital neutropenia (Shwachman Diamond and GATA2 syndromes). Regarding adult AML without genetic predisposition, we study the most frequent age-related pre-leukemic mutations (TET2, DNMT3A, and TP53 mutations). Our goal is to understand how these acquired lesions can provide a selective advantage to mutant cells over normal hematopoietic cells, and then an increased probability for a clonal evolution to AML. Overall, our data indicate that the first pre-leukemic mutations will dictate, through distinct modifications of the crosstalk between hematopoietic stem cells and their micro-environment, the selection of distinct subsequent clonal events, leading to various type of AMLs. 

     

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