Pathogenesis of polycythemia vera.

Abstract

Overproduction of erythroid cells in PV is particular in that it occurs in the absence of a recognizable physiologic stimulus, since circulating serum levels of Epo are normal or lower than normal. Genetic analysis as well as in vitro studies, have established an essential role for Epo in the survival and maturation of committed erythroid progenitors. Epo initiates its cellular response by binding to the Epo receptor (EpoR) expressed on the surface of immature erythroblasts. Following ligand binding, EpoR is known to activate a cytoplasmic protein tyrosine kinase, Jak2 which triggers a signal transduction cascade that leads to the development of early erythroid progenitors into mature erythroblast cells. Although the mechanism underlying the increased erythroid production in PV is not well understood, a number of causes have recently came for which may provide insights not only for the pathogenesis of PV but also for a fundamental biological process: the mechanism whereby a multipotential stem cell gives rise to a particular cell lineage.