Characterization of the Hematopoietic Stem Cell in the Peripheral Blood of Patients with Idiopathic Myelofirosis
Abstract
The clinical course of patients with Philadelphia chromosome negative myeloproliferative disorder (MPD) 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 (EPC). Some EPC have been shown to share a number of features associated with monocytes while other more primitive progenitor cells produce EC in vitro exclusively. The cells which share features of monocytes and endothelial cells have been termed angiogenic monocytes (AM). Reduced levels of AM progenitor cells have been reported to be predictive of atherosclerotic disease progression. AM progenitor cells were assayed in vitro from the peripheral blood mononuclear cells (MNC) of MPD patients. AM colonies were plucked and analyzed for EC and hematopoietic cell markers, JAK2V617F and their ability to incorporate into vascular endothelium following their transplantation into immunodeficient mice (NODISCID). MPD AM colonies that were detected were uniformly JAK2V617F positive and produced cells that expressed phenotypic markers characteristic of both monocytes and EC. Reduced numbers of AM colonies were present in the blood of MPD patients with a high JAK2V617F burden (>50%), (p<O.Ol). Transplanted AM were able to contribute to the vascular endothelium of NODISCID mice. These studies suggest that reduced numbers of circulating AM progenitors contribute to the propensity to develop thrombotic complications in MPD patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2008
- Accession Number
- ADA499648
Entities
People
- Ronald Hoffman
Organizations
- Icahn School of Medicine at Mount Sinai