Interleukin 3 enhances the cytotoxic activity of 1-β-D-arabinofuranosylcytosine (ara-C) on acute myeloblastic leukaemia (AML) cells

We have evaluated the possibility of enhancing the cell killing effect of ara-C on AML blasts by increasing their proliferative activity with haemopoietic growth factors. Leukaemic cells from AML patients were incubated for 3 d in liquid culture in the presence or in the absence of the human recombinant growth factors IL-1β (5 U/ml) and IL-3 (3 U/ml), and subsequently exposed to ara-C (3 μg/ml) for the last 24 h. The number of residual leukaemic stem cells was evaluated by a clonogenic assay in semisolid medium. The results showed that ara-C exposure inhibits the proliferation of a higher proportion of clonogenic cells in cultures pretreated with growth factors than in the controls (mean inhibitory values: in the absence of growth factors = 49.8%; with IL-1β=58.3%; with IL-3 78.9%). The effect was statistically significant only when IL-3 was used as a growth factor. The results suggest that haemopoietic growth factors may help to improve the therapeutic index of cytostatic agents.