Comparative Mutational Profiling of Hematopoietic Progenitor Cells and Circulating Endothelial Cells (CECs) in Patients with Primary Myelofibrosis.

A role of endothelial cells (ECs) in Primary Myelofibrosis (PMF) was supposed since mutation was found in endothelial precursor cells (EPCs) and in ECs captured by laser microdissection. By Cell Search method, the circulating endothelial cells (CECs) from 14 PMF patients and 5 healthy controls have been isolated and compared by NGS with CD34+Hematopoietic stem and progenitors cells (HSPCs) for panel of 54 myeloid-associated mutations. PMF patients had higher levels of CECs. No mutation was found in HSPCs and CECs from controls, while CECs from PMF patients presented several somatic mutations. 72% of evaluable patients shared at least one mutation between HSPCs and CECs. 2 patients shared the mutation, together with , , and , , respectively. 6 out of 8 shared only NON MPN-driver mutations: and in one case; individual paired mutations in , , , and , in the other cases. In conclusion, 70% of PMF patients shared at least one mutation between HSPCs and CECs. These latter harbored several myeloid-associated mutations, besides mutation. Our results support a primary involvement of EC in PMF and provide a new methodological approach for further studies exploring the role of the "neoplastic" vascular niche.