Interferon or down-regulates telomerase reverse transcriptase and telomerase activity in human malignant and nonmalignant hematopoietic cells

Recently, the derepressed expression of the catalytic subunit of telomerase , human telomerase reverse transcriptase (hTERT), the enzyme that elongates telomeres, has been implicated as an important step in the immortalization process. The exact regulation of hTERT expression, which is the rate-limit ing factor for telomerase activity, is at present unclear. As transformed c ells seem to be dependent on a constitutive telomerase activity, the availa bility of inhibitors would potentially be of great value in antineoplastic therapy, Interferons (IFNs) have been successfully used in the treatment of several forms of malignancies, but the underlying molecular mechanisms res ponsible for the antitumor activity are poorly defined. In this study we ha ve investigated the effects of IFNs on hTERT expression and telomerase acti vity. We found that IFN alpha rapidly (commonly within 4 hours) and signifi cantly down regulates the expression of hTERT and telomerase activity in a number of human malignant hematopoietic cell lines, primary leukemic cells from patients with acute leukemia as well as T-lymphocytes from healthy don ors. This effect of IFN-alpha did not seem to depend on IFN-alpha -mediated cell growth arrest or alterations in c-myc expression. The finding that IF N induces a repression of hTERT and a decrease in telomerase activity sugge sts a novel mechanism that may play a significant role in the antitumor act ion of IFN. (C) 2000 by The American Society ct Hematology.