Recombinant human granulocyte colonystimulating factor enhanced cytotoxicity of Ara-C In Ara-C-resistant leukemic cells from a patient with biphenotypic leukemia in cell kinetic quiescence

Abstract

In vitro preincubation with recombinant granulocyte colony-stimulating factor(rhG-CSF, 100 ng/ml) enhanced the cytotoxocity of 1-β- d-arabinofuranosylcytosine(Ara-C) in leukemic cells resistant to Ara-C from a patient with biphenotypic leukemia. Treatment of the cells with rhG-CSF resulted in a 17-fold increase in DNA synthesis, 4.6-fold increase in percentage of S-phase, and a twofold increase in Ara-CTP formation. Maximal effect was observed at 72 h of incubation. Combination chemotherapy with rhG-CSF and Ara-C to the patient showed remarkable cytoreduction. These results indicate that recruitment of resistant leukemic cells in cell kinetic quiescence is inducible by rhG-CSF and that it is possible enhancement of the cytotoxocity to cell cycle-specific drugs such as Ara-C.