Role of the Antiapoptotic Protein Bcl-xL in the Pathogenesis of Polycythemia Vera

Hematopoietic progenitor cell survival is mediated via the interaction of stimulatory and inhibitory hematopoietins (i.e., cytokines, growth factors) and their receptors. Among these, erythropoietin (EPO) is the principal growth factor that promotes the survival of erythroid progenitors. Analysis of mutant mice has clearly established an essential role for EPO and its receptor (EPOR) in erythroid development. In embryos of mice deficient in EPO or the EPOR, definitive erythropoiesis is completely impaired and liver tissue contains increased numbers of nucleated erythroid cells undergoing apoptosis[2]. In addition, in vitro studies show that in the absence of EPO, erythroid progenitors die and their genomic DNA is degraded into oligonucleosomal fragments, a feature of apoptotic cell death [2]. Based on these data, a model has been proposed whereby the concentration of circulating EPO controls the number of erythroid progenitors that survive by inhibiting apoptotic cell death [3]. Although the precise mechanisms by which EPO suppresses apoptosis of erythroid cells remains to be elucidated, several recent publications have thrown some interesting light on this issue.