NF-E2 overexpression delays erythroid maturation and increases erythrocyte production.
Br J Haematol
; 146(2): 203-17, 2009 Jul.
Article
in En
| MEDLINE
| ID: mdl-19466964
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polycythemia Vera
/
Erythrocytes
/
Erythropoiesis
/
NF-E2 Transcription Factor
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Br J Haematol
Year:
2009
Document type:
Article
Affiliation country: