Molecular aspects of polycythemia vera (review)

Abstract

Polycythemia vera (PV) is a rare, progressive myeloproliferative disorder thought to originate from the clonal expansion of a multipotent haemopoietic stem cell. This disease is characterised by hyperproliferation of the erythroid, myeloid and megakaryocyte lineages in the early phase, anaemia and fibrosis in the spent phase, and with a significant number of patients developing acute myeloid leukaemia (AML) in the final phase. Studies investigating the growth factor requirements of committed progenitors have shown hypersensitivity to a number of haemopoietic growth factors (HGF) in vitro and several HGF receptor and signalling molecule alterations have been reported. The findings to date, however, are unable to account for the transformation of a primitive stem cell and the many alterations to growth factor responses seen in PV progenitors. Identification of the primary lesion that leads to the pathogenesis of PV is of major importance given the profound effects on regulation of the haemopoietic stem cell compartment. In this article we focus on characteristics of the disease, research findings to date and possible mechanisms to explain altered growth factor responses, receptor alterations and signalling abnormalities in PV.