The present project aims to experimentally test the hypothesis that JAK2V617F mutated endothelium in primary myelofibrosis (PMF) we discovered in 2013 represents an embryonic-like hemogenic endothelium and is part of the malignant stem cell pool that give rise to clonal hematopoiesis. The hypothesis stems from the recent evidence that JAK2 mutation in PMF patients is acquired in utero or childhood. The experimental plan of the project is 1) to separate mature endothelial cells from peripheral blood of PMF patients for morphological, molecular, functional characterization and clonogenic assays; 2) to assay the megakaryocyte, erythroid, granulocyte and endothelial clonogenic potential of the mature endothelial cells of patients with PMF. The potential to form colonies will be the documentation that a fraction of mature endothelial cells of patients with PMF have the characteristics of embryonic hemogenic endothelium and might act as the cell of origin of PMF.