[Enhanced sensitivity to cytosine arabinoside by combined stimulation of steel factor and GM-CSF in a factor-dependent leukemic cell line, MO7e--in terms of a possible clinical application to AML treatment]

Rinsho Ketsueki. 1993 Jul;34(7):821-8.
[Article in Japanese]

Abstract

In normal hematopoiesis, granulocyte macrophage-colony stimulating factor (GM-CSF) is known to stimulate the proliferation and differentiation of myelo-monocytoid lineage, while Steel factor (SLF) has been supposed to support the proliferation of more primitive hematopoietic progenitors including stem cells. We investigated the stimulatory effect of SLF and GM-CSF in twelve cases of acute myeloid leukemia (AML) cells in vitro by MTT assay. In 10 out of 12 cases, SLF or GM-CSF stimulated the proliferation of leukemic cells in short term liquid culture. In 7 out of these 10 cases, the leukemic cells responded to both cytokines. To investigate the possibility of the clinical application of these cytokines by combination with cell cycle-specific anti-tumor reagents, we assessed the effects of SLF and GM-CSF on the modulation of the cell cycle and sensitivity against cytosine arabinoside (ara-C) in a human factor-dependent leukemic cell line, MO7e. Flow cytometric analysis revealed the effect of cell recruitment into the cell cycle in the quiescent MO7e cells by exposure to these cytokines. The drug-sensitivity test using the MTT assay system demonstrated that pre-treatment with each cytokine enhanced sensitivity of ara-C. Furthermore, by combination of SLF and GM-CSF, the ara-C sensitivity was significantly wore graty enhanced than by each cytokine alone. These data suggest that combined pre-treatment with SLF and GM-CSF may provide new benefits for cure-oriented chemotherapy of AML followed by bone marrow transplantation or peripheral blood stem cell transplantation.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Cycle / drug effects
  • Cytarabine / pharmacology*
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Cell Growth Factors / pharmacology*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Middle Aged
  • Stem Cell Factor
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / pathology

Substances

  • Hematopoietic Cell Growth Factors
  • Stem Cell Factor
  • Cytarabine
  • Granulocyte-Macrophage Colony-Stimulating Factor