NF-E2 overexpression delays erythroid maturation and increases erythrocyte production

Manuel Mutschler, Angela S. Magin, Martina Buerge, Roland Roelz, Daniel H. Schanne, Britta Will, Ingo H. Pilz, Anna Rita Migliaccio, Heike L. Pahl

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)203-217
Number of pages15
JournalBritish Journal of Haematology
Volume146
Issue number2
DOIs
StatePublished - Jul 2009
Externally publishedYes

Fingerprint

Polycythemia Vera
Erythrocytes
Polycythemia
Erythropoietin
NF-E2 Transcription Factor
Glycophorin
Erythroid Precursor Cells
Erythroid Cells
Erythrocyte Count
Cell Proliferation
Growth

Keywords

  • CD34 cells
  • Myeloproliferative disorders
  • Transcription factors

ASJC Scopus subject areas

  • Hematology

Cite this

NF-E2 overexpression delays erythroid maturation and increases erythrocyte production. / Mutschler, Manuel; Magin, Angela S.; Buerge, Martina; Roelz, Roland; Schanne, Daniel H.; Will, Britta; Pilz, Ingo H.; Migliaccio, Anna Rita; Pahl, Heike L.

In: British Journal of Haematology, Vol. 146, No. 2, 07.2009, p. 203-217.

Research output: Contribution to journalArticle

Mutschler, M, Magin, AS, Buerge, M, Roelz, R, Schanne, DH, Will, B, Pilz, IH, Migliaccio, AR & Pahl, HL 2009, 'NF-E2 overexpression delays erythroid maturation and increases erythrocyte production', British Journal of Haematology, vol. 146, no. 2, pp. 203-217. https://doi.org/10.1111/j.1365-2141.2009.07742.x
Mutschler, Manuel ; Magin, Angela S. ; Buerge, Martina ; Roelz, Roland ; Schanne, Daniel H. ; Will, Britta ; Pilz, Ingo H. ; Migliaccio, Anna Rita ; Pahl, Heike L. / NF-E2 overexpression delays erythroid maturation and increases erythrocyte production. In: British Journal of Haematology. 2009 ; Vol. 146, No. 2. pp. 203-217.
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