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    Normal and Pathological hematopoiesis

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    Team leaders

    Hematopoiesis refers to the process leading to the continuous production of blood cells during life. In the bone marrow, it implicates rare hematopoietic stem cells capable of self-renewing and progenitors which expand and differentiate into diverse lineages. The team, with the clinical and biological departments of hematology at Cochin hospital, analyses the mechanisms responsible for stem cell maintenance, oncogenic transformation of stem and progenitor cells in myeloid leukemias and myelodysplastic syndromes and resistance to anti-leukemic drugs.

     

    Objectives

    • Stem cell maintenance – implication of the post-transcriptional regulation of gene expression

    The basic research conducted by I Dusanter & E Lauret explores the stem cell biology in normal adult hematopoiesis and has identified two RNA binding proteins (RBP), Pumilio1/2, as key regulators of stemness. To understand the molecular mechanisms of stemness regulation, Pumilio1/2 partners and targets are investigated in the context of normal and leukemic cells. The impact of overexpressed Pumilio1/2 on gene expression profiles in leukemic cells is studied using comparative transcriptomic, proteomic, and ribosome profiling approaches.

    • Myelodysplastic syndromes – mechanisms of oncogenic transformation

    Myelodysplastic syndromes are hematopoietic stem cell disorders with a propensity to leukemic transformation. Recurrent mutations and microenvironment interactions drive the disease initiation and clonal hematopoietic stem and progenitor cell amplification. Mechanisms underlying clonal selection are investigated using in vitro cell line models and patient-derived xenografts of hematopoietic and mesenchymal cells to immunodeficient mice (E Lauret, O Kosmider, M Fontenay).

    • Acute myeloid leukemia – mechanisms of resistance to anti-leukemic drugs

    Important deregulation of translation and metabolic pathways has been deciphered in acute myeloid leukemia by the team leading to the proposal of targeted therapies. Large-scale screens are performed to discover intrinsic mechanisms of resistance to chemotherapy in the context of the bone marrow microenvironment. This will help deciphering new AML subgroups and identifying prognostic / theranostic biomarkers (E Lauret, N Chapuis, D Bouscary).

     

    Main Publications

     

    Team’s news

    Labellisations

    Research project

    The team is a WP2 partner of the H2020 MDS-RIGHT project aiming at comparing existing health care interventions including methods of molecular diagnosis and at defining and implementing more effective and safer interventions for elderly European citizens with anaemia and/or lower-risk MDS, the project aims to lead to better treatment compliance and more (cost-) effective use of healthcare resources. https://mds-europe.eu/right

    Patent

    A biomarker of diagnosis and response to treatment in acquired sideroblastic anemia: INSERM-transfert EP 19305047.3 (16/01/2019)

    Meetings

    Organisation de la Journée hématologie du PRES – next 17 octobre 2019

     

    Contacts


    Bâtiment G Roussy 7è étage pièce 732
    Tel :  +33 (0)1 58 41 20 04/(0)1 40 51 64 04


    Bâtiment G Roussy 7è étage pièce 732
    Tel :  +33 (0)1 58 41 29 46/(0)1 40 51 64 04