1) We study the dialogue between mesenchymal stromal cells (MSC) and CD34 + hematopoietic stem cells (HSC) via extracellular vesicles (EVs). We show a deregulation of the miRnome in the MSC and the HSC with some interesting targets.

2) We also show in a subgroup of myelodysplastic syndrome, chronic myelomonocytic leukemia (CMML) that the small extracellular vesicles derived from the tumoral MSC and the monocytes carry a procoagulant climate within the endosteal tumor niche. Suppression of the tissue factor (TF)-FVII pathway inhibits CMML EVs procoagulant activity. This procoagulant environment could favour LSC homeostasis.

3) There is a great deal of data on innate immune system deregulation and inflammatory signaling that would affect the cells of the medullary niche. Indoleamine 2,3-dioxygenase-1 (IDO / IDO1), is a key enzyme, first step of the kynurenine pathway. Activation of IDO leads to the death of effector T cells, Natural Killer (NK) cells, and favours the differentiation of regulatory T-cells, and the activation of suppressive myeloid cells(MDSCs). We are deciphering the immune suppressive cells in the medullar niche of MDS and their relationship with IDO.

4) And lastly, we describe a PDX mouse model we have set for myelodysplas ;c syndromes, which recapitulates exactly the molecular hierarchy of the pathological clones. It is an interesting in vivo model for future therapeutic use and for microenvironment studies.

Contact : karin.sadoul@univ-grenoble-alpes.fr