DDX41 encodes for a cytosolic viral DNA sensor, involved in the IFN-I response to infection. Intriguingly, germline mutations in the DDX41 gene were associated with impaired hematopoiesis, cytopenia, with a risk to develop MDS/AML.

Whether and how DDX41 mutation affects the bone marrow immune landscape is unknown. Our team associated to Pr. M. Sébert proposes to investigate the bone marrow immune features of DDX41-related MDS/AML patients.

We will characterize the phenotype and function of the lymphocytes and the Mesenchymal Stromal Cells (MSC), both cell subsets involved in modulating immunosurveillance against leukemic cells. DDX41-related MDS/AML patients’ blood and bone marrow paired samples will be analyzed with 40-markers spectral flow-cytometry panels specific for T, B and NK lymphocytes subsets, leukemic cells and MSC.

T and NK cell polyfunctionality (cytokine release and cytotoxicity) will be tested. MSCs will be analyzed for the expression of immunomodulating membrane-bound and soluble factors.

This project will produce preliminary data about the impact of the DDX41 deficiency on the anti-tumoral immunity in the bone marrow microenvironment in MDS/AML patients.