Treatment with interferon-α preferentially reduces the capacity for amplification of granulocyte-macrophage progenitors (CFU-GM) from patients with chronic myeloid leukemia but spares normal CFU-GM

Abstract

The biological target for interferon (IFN)-α in chronic myeloid leukemia (CML) is unknown, but one possibility is that amplification of granulocyte-macrophage colony-forming cells (CFU-GM) is reduced. Replating CFU-GM colonies and observing secondary colony formation provides a measure of CFU-GM amplification. Amplification of CML, but not normal, CFU-GM in vitro was significantly inhibited by IFN-α (P = 0.02). In 5 out of 15 CML cases studied by fluorescence in situ hybridization, in vitro treatment with IFN-α increased the proportion of CFU-GM, which lacked BCR-ABL. The ability of patients' CFU-GM to amplify, and suppression of this ability by IFN-α, predicted responsiveness to IFN-α therapy in 86% of cases. Investigation of patients on treatment with IFN-α showed a threefold reduction in CFU-GM amplification in responders (P = 0.03) but no significant change in nonresponders (P = 0.8). We conclude that IFN-α preferentially suppresses amplification of CML CFU-GM to varying degrees. The differing in vitro sensitivities to IFN-α and growth kinetics of individual patients' cells could help differentiate those who will or will not benefit from treatment with IFN-α.