Treatment with Interferon- a Preferentially Reduces the Capacity for Amplification of Granulocyte-Macrophage Progenitors (CFU-GM) from Patients with Chronic Myeloid Leukemia but Spares Normal CFU-GM

The biological target for interferon (IFN)a 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 IFNa ( P 5 0.02). In 5 out of 15 CML cases studied by fluorescence in situ hybridization, in vitro treatment with IFNa increased the proportion of CFU-GM, which lacked BCRABL. The ability of patients’ CFU-GM to amplify, and suppression of this ability by IFNa , predicted responsiveness to IFNa therapy in 86% of cases. Investigation of patients on treatment with IFNa showed a threefold reduction in CFU-GM amplification in responders ( P 5 0.03) but no significant change in nonresponders ( P 5 0.8). We conclude that IFNa preferentially suppresses amplification of CML CFU-GM to varying degrees. The differing in vitro sensitivities to IFNa and growth kinetics of individual patients’ cells could help differentiate those who will or will not benefit from treatment with IFNa . ( J. Clin. Invest. 1998. 102: 710–715.)