NF-E2 overexpression delays erythroid maturation and increases erythrocyte production

Autor: Ingo H. Pilz, Heike L. Pahl, Britta Will, Roland Roelz, Anna Rita Migliaccio, Angela S. Magin, Daniel H. Schanne, Manuel Mutschler, Martina Buerge
Rok vydání: 2009
Předmět:
Zdroj: British Journal of Haematology. 146:203-217
ISSN: 1365-2141
0007-1048
DOI: 10.1111/j.1365-2141.2009.07742.x
Popis: 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.
Databáze: OpenAIRE
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