Chronic Myelocytic Leukemia and Interferon: Pathophysiological, Clinical and Therapeutical Aspects

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Overview

Studies on the effect of recombinant human interferon (rIFN) on the growth of colonies of multi potential hematopoietic progenitors have demonstrated that IFN inhibits the growth of these cells in culture. The inhibitory effect of IFN was more pronounced in multilineage colony forming cells (CFU-GEMMT) of marrow cells of patients with chronic myelogenous leukemia (CML) compared with stern cells of normal marrow. T cell colony formation (CFU-TL) of phi_positive T cells obtained from primary multilineage hematopoietic colonies was inhibited by rIFN. Inhibition of T cell colony formation of Phi T cells was more profound by IFN compared with secondary T cells of healthy individuals. Southern blot analysis of secondary T cells from normal individuals revealed a germ line pattern when examined for T cell receptor (TcR) gene re arrangements using the cDNA of the beta chain. Subcloned Phi T cells of one patient with CML demonstrated gene rearrangements of the TcR. We also demonstrated the disappearance of phi_positive multilineage hematopoietic colonies when marrow cells were preincubated with IFN and subsequently cultured in the presence of IFN. The cytoconversion of the Phi chromosome in metaphases obtained from individually analyzed multilineage hematopoietic colonies suggests that IFN might allow the restoration of nonclonal hematopoiesis in patients with CML. Acknowledgement. Supported in part by Deutsche Forschungsgemeinschaft and the Medical Research Council of Canada. References 1. Koeffler HP, Golde DW (1981) Chronic myelogenous 1eukelnia - new concepts.