HEMATOPOIESIS Brief report Constitutive activation of STAT5 and Bcl-xL overexpression can induce endogenous erythroid colony formation in human primary cells

The biologic hallmark of polycythemia vera (PV) is the formation of endoge-nous erythroid colonies (EECs) with an erythropoietin-independent differentia-tion. Recently, it has been shown that an activating mutation of JAK2 (V617F) was at the origin of PV. In this work, we studied whether the STAT5/Bcl-xL path-way could be responsible for EEC forma-tion. A constitutively active form of STAT5 was transduced into human ery-throid progenitors and induced an eryth-ropoietin-independent terminal differen-tiation and EEC formation. Furthermore, Bcl-xL overexpression in erythroid pro-genitors was also able to induce ery-throid colonies despite the absence of erythropoietin. Conversely, siRNA-mediated STAT5 and Bcl-xL knock-down in human erythroid progenitors inhibited colony-forming unit–erythroid (CFU-E) formation in the presence of Epo. Alto-gether, these results demonstrate that a sustained level of the sole Bcl-xL is ca-pable of giving rise to Epo-independent erythroid colony formation and suggest that, in PV patients, JAK2V617F may induce EEC via the STAT5/Bcl-xL pathway