IL-6/sIL-6R and SDF-1/CXCR4 axis in essential thrombocythemia

MARTA RF

París

Conferencia; Seminario de la UMR1009, INSERM; 2010

UMR1009, INSERM

This presentation is about my reseach and that of some fellows of our lab As you know, megakaryocyte development and maturation depend on some cytokines and chemokines, mainly TPO, but some others also have a rol. Among them, in the last years we were working on IL-6 and SDF-1 and specifically in their receptors, as well as the role of monocytes in the pathophysiology of essential thrombocythemia. Overall, our conclusions in this area were 1-that monocytes and platelets are likely to be the responsables for the increased sIL-6R plasmatic increase in essential thrombocycthemic patients. 2-Abnormal regulation of IL-6 receptors are demonstrated by -The upregulation of IL-6R on monocyte membrane during cell culture. -Increased sIL-6R synthesis. -Abnormal cooperation between monocytes and lymphocyts in sIL-6R production. 3-Increased alfaIL-2R on monocyte membrane according to the severity of thrombosis and JAK2 mutalional status. Regarding SDF-1/CXCR4 axis, we have found a decrease in CXCR4 only en the later stage of megakaryocytic lineage and on platelet membrane. This abnormality is related to CXCR4 RNA decrease, the whole platelet population have the abnormality and the decrease leads to an abnormal platelet response to SDF-1.