Impact Of The Jak2v617f Mutation On The Hemato-Endothelial Differentiation In An Induced Pluripotent Stem Cells (Ipsc) Model

Background: Philadelphia-negative Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by the acquisition of genetic alterations, the most frequent being the JAK2V617F mutation. Clinical complications include thrombo-hemorrhagic events and progression to either myelofibrosis or acute leukemia. MPNs are also associated with extramedullary hematopoiesis and increased vascularity in the spleen and bone marrow. Such neo-angiogenesis has been reported to involve the development of new microvessels through the local expansion of endothelial cells (ECs). Though JAK2V617F mutation was detected in ECs of hepatic venules of MPN patients with Budd-Chiari syndrome and in ECs derived from splenic capillaries, the presence of JAK2V617F in the endothelial lineage remains debatable and demonstration of hematopoietic and endothelial differentiation from progenitor cells harboring this mutation is lacking. We used a JAK2V617F iPSC line to assess the impact of this mutation on hematopoietic and endothelial differentiation.