In vivo and in vitro treatment of HTLV-1 and HTLV-2 infected cells with arsenic trioxide and interferon-alpha.
Adult T-cell leukemia/lymphoma (ATLL) is a malignant lymphoproliferation of mature activated T-cells, mostly CD4, which develops after a long period of latency following Human T cell Lymphotropic virus Type 1 infection. It is characterized by the clonal integration of one or more HTLV-1 proviruses in the tumor cells. There are 4 major subtypes of ATLL: a smoldering type, a chronic type, a lymphoma type and a leukemic/acute type. The survival rate of ATLL patients, especially those who develop the acute leukemic or lymphomas forms, is very poor and such a tumor remains one of the most severe lymphoproliferations. Treatment of ATLL patients using conventional chemotherapy has very limited benefit, since HTLV-1 transformed cells are resistant to most apoptosis-inducing agents. Recently, antiretroviral therapy using the combination of zidovudine (AZT) and interferon alpha (IFN-alpha) has been shown to induce a high complete remission rate and to prolong the survival of ATLL patients. Based on the current physiopathology, other drugs such as arsenic trioxide combined to IFN-alpha have also been demonstrated to synergize in vitro for inducing apoptosis in HTLV-1 infected T cells. Such drugs have now been used in vivo for treating ATLL patients. Both in vitro and in vivo data will be discussed.
Mahieux
Renaud
R
Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pateur, Paris cedex 15, France. rmahieux@pasteur.fr
Hermine
Olivier
O
D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D004357:Drug Synergism; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects; D015367:Human T-lymphotropic virus 2 / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000494:pharmacology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000821:virology; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010087:Oxides / Q000008:administration & dosage* / Q000494:pharmacology; D014412:Tumor Virus Infections / Q000188:drug therapy* / Q000821:virology
D044966:Anti-Retroviral Agents; D001152:Arsenicals; D016898:Interferon-alpha; D016328:NF-kappa B; D010087:Oxides; D000077237:Arsenic Trioxide