title: NF-E2 overexpression delays erythroid maturation and increases erythrocyte production.
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.
authors.affiliation: Department of Experimental Anaesthesiology, Centre for Clinical Research, University Hospital Freiburg, Freiburg 79106, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mutschler
authors.forename: Angela S
authors.initials: AS
authors.lastname: Magin
authors.forename: Martina
authors.initials: M
authors.lastname: Buerge
authors.forename: Roland
authors.initials: R
authors.lastname: Roelz
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Schanne
authors.forename: Britta
authors.initials: B
authors.lastname: Will
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Pilz
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Migliaccio
authors.forename: Heike L
authors.initials: HL
authors.lastname: Pahl
mesh_terms: 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
chemical_list: D018952:Antigens, CD34; D050983:NF-E2 Transcription Factor