Effects of interferon gamma on native human acute myelogenous leukaemia cells

T cell targeting immunotherapy is now considered a possible strategy in acute myelogenous leukaemia (AML), and IFN gamma release may then contribute to the antileukaemic effects. We investigated the effects of IFN gamma on native human AML cells. Normal T cells could be activated to release IFN gamma in the presence of AML cells. Furthermore, high levels of CD119 (IFN gamma receptor alpha chain) expression were observed for all 39 patients examined. Receptor expression was decreased after exposure to exogenous IFN gamma, and receptor ligation caused Stat1 phosphorylation but no phosphorylation of the alternative messengers Erk1/2. The effect of exogenous IFN gamma on AML blast proliferation was dependent on the local cytokine network and IFN gamma (1) inhibited proliferation in the presence of exogenous IL1 beta, GM-CSF, G-CSF and SCF; (2) had divergent effects in the presence of IL3 and Flt3 (65 patients examined); (3) inhibited proliferation in the presence of endothelial cells but had divergent effects in the presence of fibroblasts, osteoblasts and normal stromal cells (65 patients examined). IFN gamma increased stress-induced (spontaneous) in vitro apoptosis as well as cytarabine-induced apoptosis only for a subset of patients. Furthermore, IFN gamma decreased the release of proangiogenic CXCL8 and increased the release of antiangiogenic CXCL9-11. We conclude that IFN gamma can be released in the presence of native human AML cells and affect AML cell proliferation, regulation of apoptosis and the balance between pro- and antiangiogenic chemokine release.