Gene expression profiles in HTLV-I-immortalized T cells: deregulated expression of genes involved in apoptosis regulation

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia, an acute and often fatal T-cell malignancy. A key step in HTLV-I-induced leukemigenesis is induction of abnormal T-cell growth and s urvival. Unlike antigen-stimulated T cells, which cease proliferation after a finite number of cell division, HTLV-I-infected T cells proliferate inde finitely (immortalized), thus facilitating occurrence of secondary genetic changes leading to malignant transformation. To explore the molecular basis of HTLV-I-induced abnormal T-cell survival, we compared the gene expressio n profiles of normal and HTLV-I-immortalized T cells using 'gene array'. Th ese studies revealed a strikingly altered expression pattern of a large num ber of genes along with HTLV-I-mediated T-cell immortalization. Interesting ly, many of these deregulated genes are involved in the control of programm ed cell death or apoptosis. These findings indicate that disruption of the cellular apoptosis-regulatory network may play a role in the HTLV-I-mediate d oncogenesis.