Effects of interleukin 3, interleukin 7, and B-cell growth factor on proliferation and drug resistance in vitro in childhood acute lymphoblastic leukemia

Growth factors have been reported to enhance the cytotoxicity of anticancer agents. In our study we investigated the capacities of interleukin 3 (IL-3 ), interleukin 7 (IL-7), low-molecular-weight B-cell growth factor (1mw-BCG F), and IL-3+7 to induce proliferation and to modulate the drug resistance of childhood acute lymphoblastic leukemia (ALL) cells. Proliferation was as sessed with the methyl-thiazole-tetrazolium (MTT) assay and other parameter s. Cellular resistance to cytarabine, thioguanine, and prednisolone was mea sured using the MTT assay. In 19 samples containing >90% leukemic cells the proliferative response and the modulation of drug resistance was markedly heterogeneous between patient samples and between growth factors. All growt h factors were able to stimulate proliferation significantly after 5 days o f culture. 1mw-BCGF was the most potent growth factor in this respect. Cyto toxicity of cytarabine and thioguanine was significantly increased by IL-7, that of thioguanine by IL-3 as well. IL-7 enhanced the cytotoxicity of thi oguanine significantly more than IL-3 and 1mw-BCGF and that of cytarabine m ore than IL-3. Cytotoxicity of prednisolone was not significantly influence d by any growth factor. In individual cases, growth factors reduced the cyt otoxicity of the drugs. IL-3+7 did not add activity to the most potent sing le growth factor in both proliferation and drug resistance measurements. Th is study shows that IL-3, IL-7, and 1mw-BCGF generally induce and occasiona lly inhibit proliferation of ALL cells. Furthermore, they may either increa se or decrease cytotoxicity of anticancer drugs. This heterogeneous respons e to growth factors concerning induction of proliferation and modulation of drug resistance should be taken into account in their clinical use.