Combination of granulocyte colony-stimulating factor and low-dose cytosinearabinoside 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 gra nulocyte colony-stimulating factor (G-CSF) plus low-dose cytosine arabinosi de (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 dif ferentiation induction of leukemia cells was observed in response to G-CSF. This suggests that most myeloid leukemia cells are able to respond to G-CS F stimulation. In addition, treatment of cells with low-dose Ara-C alone re sulted in the enhancement of myeloid specific antigens expression in 16 cas es (64 %). Treatment of leukemia cells with higher concentrations of Ara-C lover 50 ng/ml) alone resulted in cytocidal effects but not in the inductio n of differentiation. Furthermore, 15 cases (60%) showed pronounced myeloid differentiation of leukemia cells after combined exposure to G-CSF plus lo w-dose Ara-C as compared with cells treated with either G-CSF or Ara-C alon e. 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 WE HI-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, an d also appears to be useful for the differentiation-base therapy of patient s with AML and MDS.