Combination of granulocyte colony-stimulating factor and low-dose cytosine arabinoside further enhances myeloid differentiation in leukemia cells in vitro.
We examined the differentiation-inducing effect on freshly isolated myeloid leukemia cells in liquid suspension culture by combined treatment with granulocyte colony-stimulating factor (G-CSF) plus low-dose cytosine arabinoside (Ara-C; 5-10 ng/ml) in 25 patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in leukemic transformation. Culture with G-CSF alone showed leukemic cell growth stimulation in 15 out of the 25 cases (60%) and induction of cell differentiation in 19 out of the 25 cases (76%), respectively. In 23 cases (92%), either growth stimulation and/or differentiation induction of leukemia cells was observed in response to G-CSF. This suggests that most myeloid leukemia cells are able to respond to G-CSF stimulation. In addition, treatment of cells with low-dose Ara-C alone resulted in the enhancement of myeloid specific antigens expression in 16 cases (64%). Treatment of leukemia cells with higher concentrations of Ara-C (over 50 ng/ml) alone resulted in cytocidal effects but not in the induction of differentiation. Furthermore, 15 cases (60%) showed pronounced myeloid differentiation of leukemia cells after combined exposure to G-CSF plus low-dose Ara-C as compared with cells treated with either G-CSF or Ara-C alone. The enhanced effect of differentiation induction by combining G-CSF plus low-dose Ara-C was also observed in a murine myeloid leukemia cell line WEHI-3B in vitro. These data suggest that treatment with G-CSF plus low-dose Ara-C is capable of inducing differentiation of leukemic cells in vitro, and also appears to be useful for the differentiation-based therapy of patients with AML and MDS.
Katagiri
T
T
First Department of Internal Medicine, Tokyo Medical University, Japan.
Miyazawa
K
K
Nishimaki
J
J
Yaguchi
M
M
Kawanishi
Y
Y
Ohyashiki
K
K
D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D003561:Cytarabine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor