[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].
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.
Gotoh
A
A
First Department of Internal Medicine, Tokyo Medical College.
Kawanishi
Y
Y
Kurosawa
K
K
Miyazawa
K
K
Ohtaka
M
M
Aizawa
S
S
Kimura
Y
Y
Yoshikawa
O
O
Toyama
K
K
D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor