title: Constitutive activation of STAT5 and Bcl-xL overexpression can induce endogenous erythroid colony formation in human primary cells.
abstract: The biologic hallmark of polycythemia vera (PV) is the formation of endogenous erythroid colonies (EECs) with an erythropoietin-independent differentiation. 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 pathway could be responsible for EEC formation. A constitutively active form of STAT5 was transduced into human erythroid progenitors and induced an erythropoietin-independent terminal differentiation and EEC formation. Furthermore, Bcl-xL overexpression in erythroid progenitors was also able to induce erythroid 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. Altogether, these results demonstrate that a sustained level of the sole Bcl-xL is capable of giving rise to Epo-independent erythroid colony formation and suggest that, in PV patients, JAK2(V617F) may induce EEC via the STAT5/Bcl-xL pathway.
authors: Unité (U) 790 Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy, Villejuif, France.
authors: Loïc
authors: L
authors: Garçon
authors: Christine
authors: C
authors: Rivat
authors: Chloé
authors: C
authors: James
authors: Catherine
authors: C
authors: Lacout
authors: Valérie
authors: V
authors: Camara-Clayette
authors: Valérie
authors: V
authors: Ugo
authors: Yann
authors: Y
authors: Lecluse
authors: Annelise
authors: A
authors: Bennaceur-Griscelli
authors: William
authors: W
authors: Vainchenker