Arsenic Trioxide for Non Acute Promyelocytic Leukemia Hematological Malignancies: A New Frontier

Arsenic trioxide (As2O3) has been confirmed to be effective in the treatment of Acute Promyelocytic Leukemia (APL). Also, encouraging results have been reported in preclinical studies and pilot clinical trials of As2O3 in other hematological malignancies such as Multiple Myeloma (MM), Myeloplastic syndromes (MDS), T-cell leukemia-lymphoma and Chronic Myelogenous Leukemia (CML). However, conflicting findings have been reported in non-APL Acute Myeloid Leukemia (AML). The mechanisms of As2O3 activity are complex, with multiple modifications of cell growth and apoptosis control regulations of pro-survival and cell defense molecules, cell cycle arrest, glutathione redox system, p53-dependent apoptotic signals; telomerase activity and caspase pathway. It is now known that other mechanisms are also involved including the immunomodulatory and angiogenesis regulation. Recently there is a trend of investigating whether tetra-arsenic tetra-sulphide will be a better alternative for the arsenic trioxide. In summary this review describes emerging information that provides new insights for As2O3 as a broad spectrum chemotherapeutic agent in the treatment of hematological malignancies beyond APL.