Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-κB activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the most recently discovered human herpesvirus. It is the aetiological agent of Kaposi's sarcoma (KS), a tumour frequently affecting AIDS patients not receiving treatment. KSHV is also a likely cause of two lymphoproliferative diseases: multicentric Castleman's disease and primary effusion lymphoma. The study of KSHV offers exciting challenges for understanding the mechanisms of virus pathogenesis, including those involved in establishing infection and dissemination in the host. To facilitate these processes, approximately one-quarter of KSHV genes encode cellular homologues or unique proteins that have immunomodulatory roles in cytokine production, apoptosis, cell signalling and the immunological synapse. The activities of these molecules are considered in the present review and the positions of their genes are mapped from a complete KSHV genome sequence derived from a KS biopsy. The understanding gained enables the significance of different components of the immune response in protection against KSHV infection to be evaluated. It also helps to unravel the complexities of cellular and immunological pathways and offers the potential for exploiting viral immunomodulators and derivatives in disease therapy.