Bay 11-7082 inhibits transcription factor NF- B and induces apoptosis of HTLV-I–infected T-cell lines and primary adult T-cell leukemia cells

Human T-cell leukemia virus type I (HTLV-I) is the causative agent of an aggressive form of leukemia designated adult T-cell leukemia (ATL). We have previously demonstrated that all T-cell lines infected with HTLV-I and primary leukemic cells from ATL patients display constitutively high activity of transcription factor NFB. In this study we showed that Bay 11-7082, an inhibitor of NFB, induced apoptosis of HTLV-I–infected T-cell lines but only negligible apoptosis of HTLV-I–negative T cells. Bay 11-7082 rapidly and efficiently reduced the DNA binding of NFB in HTLV-I–infected T-cell lines and downregulated the expression of the antiapoptotic gene, Bcl-xL, regulated by NFB, whereas it had little effect on the DNA binding of another transcription factor, AP-1. Although the viral protein Tax is an activator of NFB, Bay 11-7082–induced apoptosis of HTLV-I–infected cells was not associated with reduced expression of Tax. Furthermore, Bay 11-7082– induced apoptosis of primary ATL cells was more prominent than that of normal peripheral blood mononuclear cells, and apoptosis of these cells was also associated with down-regulation of NFB activity. Our results indicate that NFB plays a crucial role in the pathogenesis and survival of HTLV-I–infected leukemic cells and that it is a suitable target for the prevention and treatment of ATL. (Blood. 2002;100:1828-1834)