In vivo and in vitro treatment of HTLV-1 and HTLV-2 infected cells with arsenic trioxide and interferon-alpha

Abstract

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.