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 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.
Garçon
Loïc
L
Unité (U) 790 Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy, Villejuif, France.
Rivat
Christine
C
James
Chloé
C
Lacout
Catherine
C
Camara-Clayette
Valérie
V
Ugo
Valérie
V
Lecluse
Yann
Y
Bennaceur-Griscelli
Annelise
A
Vainchenker
William
W