Circulating angiogenic monocyte progenitor cells are reduced in JAK2V617F high allele burden myeloproliferative...

The clinical course of patients with Philadelphia chromosome negative myeloproliferative disorder is frequently complicated by thrombotic events. Post-natal vasculogenesis has been proposed to play a critical role in angiogenesis by acting through a hierarchy of endothelial progenitor cells. Some endothelial progenitor cells have been shown to share a number of features associated with monocytes while other more primitive progenitor cells produce endothelial cells in vitro exclusively. The cells which share features of monocytes and endothelial cells have been termed angiogenic monocytes. Reduced levels of angiogenic monocyte progenitor cells have been reported to be predictive of atherosclerotic disease progression. Angiogenic monocyte progenitor cells were assayed in vitro from the peripheral blood mononuclear cells of myeloproliferative disorder patients. Angiogenic monocyte colonies were plucked and analyzed for endothelial cells and hematopoietic cell markers, JAK2V617F and their ability to incorporate into vascular endothelium following their transplantation into non-obese diabetic, severe combine immunodeficient mice. Myeloproliferative disorder angiogenic monocyte colonies that were detected were uniformly JAK2V617F positive and produced cells that expressed phenotypic markers characteristic of both monocytes and endothelial cells. Reduced numbers of angiogenic monocyte colonies were present in the blood of myeloproliferative disorder patients with a high JAK2V617F burden (>50%), (p<0.01). Transplanted angiogenic monocytes were able to contribute to the vascular endothelium of non-obese diabetic, severe combine immunodeficient mice. These studies suggest that reduced numbers of circulating angiogenic monocyte progenitors contribute to the propensity to develop thrombotic complications in myeloproliferative disorder patients.