[Successful treatment of acute non-lymphoblastic leukemia from myelodysplastic syndrome by combination of human macrophage colony-stimulating factor (M-CSF) and low dose cytosine arabinoside: M-CSF-induced proliferation and tyrosine phosphorylation in leukemic blasts].

An 84-year-old woman was admitted with acute non-lymphoblastic leukemia transformed from myelodysplastic syndrome. We examined the signal transduction of the leukemic blasts. Stimulation of the blasts by macrophage colony-stimulating factor (M-CSF) resulted in tyrosine phosphorylation of several cellular proteins. In vitro proliferation of leukemic blasts was stimulated by M-CSF, but not by granulocyte colony-stimulating factor. Based upon these findings, combined therapy with M-CSF and low dose cytosine arabinoside (ara-C) was successful. After her recovery, we confirmed marked reduction of blasts and disappearance of M-CSF-responsive cells. These results suggest that M-CSF could enhance the cytotoxic effect of ara-C on leukemic blasts via its intracellular signaling pathway linked to proliferation.