NEOPLASIA Constitutive Activation of NF-kB 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 nuclear translocalization of transcription factor NF-kB, which is proposed to play a crucial role in the transformation of T cells by HTLV-I. However, the HTLV-I genes including Tax are not expressed significantly in primary leukemic cells from ATL patients. In this study, we examined the basis for NF-kB activation in freshly isolated leukemic cells from ATL patients. We found that leukemic cells from ATL patients, like HTLV-I–infected T-cell lines, display constitutive NF-kB DNA binding activity and increased degradation of IkBa (an inhibitor of NF-kB). Whereas the NF-kB binding activity in Tax-expressing T-cell lines consisted mostly of p50/c-Rel, fresh ATL samples contained p50/p50 and p50/p65 heterodimers. One T-cell line derived from ATL leukemic cells, TL-Om1, displayed constitutive NF-kB activity, as well as enhanced degradation of IkBa, despite the lack of detectable Tax expression. Interestingly, the NF-kB in TL-Om1 consists of p50/p50 and p50/p65 like that in fresh primary leukemic cells. Our results suggest that activation of NF-kB occurs through a Tax-independent mechanism in leukemic cells of ATL patients, possibly due to differential NF-kB subunit activation. r 1999 by The American Society of Hematology.