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  • Title: Treatment of acute promyelocytic leukemia with arsenic trioxide: clinical and basic studies.
    Author: Zhao WL, Chen SJ, Shen Y, Xu L, Cai X, Chen GQ, Shen ZX, Chen Z, Wang ZY.
    Journal: Leuk Lymphoma; 2001; 42(6):1265-73. PubMed ID: 11911407.
    Abstract:
    Arsenic trioxide (As2O3) has recently been identified as an effective drug in the treatment of newly diagnosed and relapsed acute promyelocytic leukemia (APL) without cross-resistance to all-trans retinoic acid and achieved complete remission rates of 80-90% according to most reports. With intravenous infusion at a dose of 0.08-0.16 mg/kg daily, a course of 28-42 days is required to induce remission. As2O3 in combination with chemotherapy as postremission therapy results in longer survival than arsenic alone. In vitro, As2O3 exerts dose-dependent dual effect; triggering apoptosis at relatively high concentration (0.5-2.0 micromol/l), which is associated with the disruption of mitochondrial transmembrane potentials, while inducing partial differentiation at low concentration (0.1-0.5 micromol/l), which might be related to retinoic acid signaling pathway. Importantly, at both concentrations, As2O3 can degrade PML (promyelocytic leukemia) -RAR alpha (retinoic acid receptor), an oncoprotein that has a central role in leukemogenesis.
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