MLF1IP promotes normal erythroid proliferation and is involved in the pathogenesis of polycythemia vera

FEBS Lett. 2017 Mar;591(5):760-773. doi: 10.1002/1873-3468.12587. Epub 2017 Feb 24.

Abstract

Myelodysplasia/myeloid leukemia factor 1-interacting protein (MLF1IP) appears to be an erythroid lineage-specific gene in mice; however, its role in normal erythropoiesis and erythropoietic disorders have not yet been elucidated. Here, we found that MLF1IP is abundantly expressed in human erythroid progenitor cells and that MLF1IP-deficiency reduces cell proliferation resulting from cell cycle arrest. Moreover, MLF1IP expression is exclusively elevated in CFU-E cells from polycythemia vera (PV) patients, and MLF1IP transgenic mice develop a PV-like disorder. Further analyses revealed that the erythroid progenitors and early-stage erythroblasts from these transgenic mice expand by up-regulating cyclin D2 and down-regulating p27 and p21. Thus, our data demonstrate that MLF1IP promotes erythroid proliferation and is involved in the pathogenesis of PV, suggesting that it might be a novel molecular target for erythropoietic disorders.

Keywords: MLF1IP; cell cycle; erythroid cells; polycythemia vera; proliferation; transgenic mice.

Publication types

  • Letter

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / pathology
  • Cell Cycle Proteins
  • Cell Differentiation
  • Cell Proliferation
  • Erythroid Precursor Cells / metabolism*
  • Erythroid Precursor Cells / pathology
  • Gene Expression Regulation
  • Histones
  • Humans
  • K562 Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Polycythemia Vera / genetics*
  • Polycythemia Vera / metabolism
  • Polycythemia Vera / pathology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transgenes

Substances

  • CENPU protein, human
  • Cell Cycle Proteins
  • Histones
  • Nuclear Proteins
  • RNA, Small Interfering