Synergistic Antiproliferative Effect of Recombinant Interferon-’y With Recombinant Interferon-a on Chronic Myelogenous Leukemia Hematopoietic

Recombinant interferons, a (rlFN-a) and ‘y (rIFN-’y), have been demonstrated to have significant antitumor activity as single agents in the treatment of chronic myelogenous leukemia (CML). Due to their possible synergistic efficacy. a combination rIFN therapy in CML has been proposed. To establish a biologic basis for this, we have studied the suppressive effects of rIFN-a and rlFN-’y on the in vitro growth of CML-derived progenitor cells (CFU-GEMM. CFUMk, BFU-E. CFU-GM). the optimal conditions for rIFN synergism. and the possible role of hematopoietic accessory cells (T-Iymphocytes and monocytes-macrophages) in mediating rIFN-induced growth inhibition. When added to unseparated bone marrow cells, rIFN-a and rIFN-’y significantly reduced colony formation. with 50% inhibition occurring at 71 and 186 U/mL for CFU-GEMM. 40 and 152 UImL for CFU-Mk. 222 and 1 .458 U/mL for BFU-E. and 119 and 442 U/mL for CFU-GM. respectively. A small amount of