Hypophosphorylation of pRB and repression of cyclin D3 and cdc25A during the granulocytic differentiation of human myeloblastic leukemia ML-1 cells

Leuk Res. 1999 Oct;23(10):901-7. doi: 10.1016/s0145-2126(99)00106-x.


Recently we succeeded in inducing synergistic differentiation toward granulocytes in human myeloblastic leukemia ML-1 cells by treatment of ATRA in combination with GM-CSF. To research the mechanism of this differentiation process, we examined expression of cell cycle-related genes that are concerned with cell growth and differentiation. We detected change to the hypophosphorylated form of pRB and down-regulation of cyclin D3 and cdc25A during induced differentiation. Furthermore, these marked alterations were hardly detected in ML-1 cells treated with ATRA or GM-CSF alone. These results suggest that hypophosphorylation of pRB and repression of cyclin D3 and cdc25A are induced synergistically by treatment with ATRA plus GM-CSF in ML-1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cyclin D3
  • Cyclins / genetics
  • Cyclins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Granulocytes / metabolism
  • Granulocytes / pathology
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / pathology*
  • Phosphorylation
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • Tumor Cells, Cultured
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism*


  • CCND3 protein, human
  • Cyclin D3
  • Cyclins
  • Retinoblastoma Protein
  • CDC25A protein, human
  • cdc25 Phosphatases