• Le 29 septembre 2022
    IRS-UN & webinar
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Seminar by Nicolas Dulphy, MCU-PH at Institut de Recherche Saint-Louis - Service Immunologie et Histocompatibilité

Myelodysplastic syndromes (MDS) are heterogeneous clonal disorders arising in the bone marrow (BM), with a high risk of progression to acute myeloid leukemia, and characterized by recurrent mutations notably in genes involved in epigenetic regulation or spliceosome machinery. BM microenvironment, contributes to MDS physiopathology. In particular, we recently showed that Natural Killer (NK) cells were defective in MDS patients, and this was associated with the presence of mutations in the methylcytosine dioxygenase TET2 in NK cells and altered interactions with mesenchymal stem/stromal cells (MSC). We suggest that MDS development and progression could benefit from perturbations in the NK-cell-mediated immunosurveillance due to the conjunction of intrinsic (TET2 mutations) and extrinsic (MSC/NK dialogue) processes. Our results underline the role of aging in the promotion of a permissive BM environment for the development of the disease, through clonal hematopoiesis and stromal sculpturing, inducing immune perturbations and pre-leukemic status.