Constitutive activation of NF-kappa B in primary adult T-cell leukemia cells

Human T-cell leukemia virus type I (HTLV-I) is an etiologic agent of adult T-cell leukemia (ATL). The viral protein Tax induces the activation and nuc lear translocalization of transcription factor NF-kappa B, which is propose d to play a crucial role in the transformation of T cells by HTLV-I. Howeve r, the HTLV-I genes including Tax are not expressed significantly in primar y leukemic cells from ATL patients. In this study, we examined the basis fo r NF-KB activation in freshly isolated leukemic cells from ATL patients. We found that leukemic cells from ATL patients, like HTLV-l-infected T-cell l ines, display constitutive NF-kappa B DNA binding activity and increased de gradation of I kappa B alpha (an inhibitor of NF-kappa B). Whereas the NF-k appa B binding activity in Tax expressing T-cell lines consisted mostly of p50/c-Rel, fresh ATL samples contained p50/p50 and p50/p65 heterodimers. On e T-cell line derived from ATL leukemic cells, TL-Om1, displayed constituti ve NF-kappa B activity, as well as enhanced degradation of I kappa B alpha, despite the lack of detectable Tax expression. Interestingly, the NF-kappa B in TL-Om1 consists of p50/p50 and p50/p65 like that in fresh primary leu kemic cells. Our results suggest that activation of NF-kappa B occurs throu gh a Tax-independent mechanism in leukemic cells of ATL patients, possibly due to differential NF-kappa B subunit activation. (C) 1999 by The American Society of Hematology.