TREATMENT WITH INTERFERON-ALPHA 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)-alpha in chronic myeloid le ukemia (CML) is unknown, but one possibility is that amplification of granulocyte-macrophage colony-forming cells (CFU-GM) is reduced. Repla ting CFU-GM colonies and observing secondary colony formation provides a measure of CFU-GM amplification. Amplification of CML, but not norm al, CFU-GM in vitro was significantly inhibited by IFN-alpha (P = 0.02 ). In 5 out of 15 CML cases studied by fluorescence in situ hybridizat ion, in vitro treatment with IFN-alpha 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-alpha, predicted responsivenes s to IFN-alpha therapy in 86% of cases. Investigation of patients on t reatment with IFN-alpha showed a threefold reduction in CFU-GM amplifi cation in responders (P = 0.03) but no significant change in nonrespon ders (P = 0.8). We conclude that IFN-alpha preferentially suppresses a mplification of CML CFU-GM to varying degrees. The differing in vitro sensitivities to IFN-alpha and growth kinetics of individual patients' cells could help differentiate those who will or will not benefit fro m treatment with IFN-alpha.