AUTOCRINE LOOP OF TUMOR-NECROSIS-FACTOR INDUCED BY INTERFERON-ALPHA IN TUMOR-CELLS FROM HAIRY-CELL LEUKEMIA

Interferon-alpha (IFN-alpha) is successfully used in the therapy of ha iry cell leukemia (HCL). We previously reported that IFN-alpha adminis tered to HCL patients stimulated the levels of tumor necrosis factor ( TNF) receptors on hairy cells. Here, we investigated the interactions between IFN-alpha and TNF, using the HCL cell line Eskol as a model. W e showed that increased levels of TNF receptors (TNFR) induced by IFN- alpha treatment were associated with stimulation of high M(r), TNFR. L ow M(r) TNFR were not detected on Eskol cells or hairy cells, either b efore or after IFN-alpha treatment. Furthermore, the expression of TNF mRNA increased in Eskol cells treated with IFN-alpha for 1-4 h as com pared to control cells. In vivo experiments showed that IFN-alpha give n to HCL patients induced both TNF mRNA expression in hairy cells and secretion of active TNF protein in patients' serum. These results prov ide evidence that IFN-alpha may induce an autocrine loop of TNF in HCL .