NF-E2 overexpression delays erythroid maturation and increases erythrocyte production.
The transcription factor Nuclear Factor-Erythroid 2 (NF-E2) is overexpressed in the vast majority of patients with polycythaemia vera (PV). In murine models, NF-E2 overexpression increases proliferation and promotes cellular viability in the absence of erythropoietin (EPO). EPO-independent growth is a hallmark of PV. We therefore hypothesized that NF-E2 overexpression contributes to erythrocytosis, the pathognomonic feature of PV. Consequently, we investigated the effect of NF-E2 overexpression in healthy CD34+ cells. NF-E2 overexpression led to a delay in erythroid maturation, manifested by a belated appearance of glycophorin A-positive erythroid precursors. Maturation delay was similarly observed in primary PV patient erythroid cultures compared to healthy controls. Protracted maturation led to a significant increase in the accumulated number of erythroid cells both in PV cultures and in CD34+ cells overexpressing NF-E2. Similarly, NF-E2 overexpression altered erythroid colony formation, leading to an increase in erythroid burst-forming unit formation. These data indicate that NF-E2 overexpression delays the early phase of erythroid maturation, resulting in an expansion of erythroid progenitors, thereby increasing the number of erythrocytes derived from one CD34+ cell. These data propose a role for NF-E2 in mediating the erythrocytosis of PV.
Mutschler
Manuel
M
Department of Experimental Anaesthesiology, Centre for Clinical Research, University Hospital Freiburg, Freiburg 79106, Germany.
Magin
Angela S
AS
Buerge
Martina
M
Roelz
Roland
R
Schanne
Daniel H
DH
Will
Britta
B
Pilz
Ingo H
IH
Migliaccio
Anna Rita
AR
Pahl
Heike L
HL
D018952:Antigens, CD34; D004912:Erythrocytes / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000378:metabolism; D004920:Erythropoiesis / Q000502:physiology*; D006801:Humans; D050983:NF-E2 Transcription Factor / Q000378:metabolism*; D011086:Polycythemia / Q000209:etiology; D011087:Polycythemia Vera / Q000097:blood / Q000209:etiology* / Q000378:metabolism
D018952:Antigens, CD34; D050983:NF-E2 Transcription Factor