Treatment of acute promyelocytic leukemia with arsenic trioxide: clinical and basic studies

Leuk Lymphoma. 2001 Nov-Dec;42(6):1265-73. doi: 10.3109/10428190109097751.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / drug effects
  • Arsenic Trioxide
  • Arsenicals / adverse effects
  • Arsenicals / pharmacokinetics
  • Arsenicals / therapeutic use*
  • Cell Differentiation / drug effects
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / mortality
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neoplasm Proteins / metabolism
  • Oncogene Proteins, Fusion / metabolism
  • Oxides / adverse effects
  • Oxides / pharmacokinetics
  • Oxides / therapeutic use*
  • Recombinant Fusion Proteins / metabolism
  • Sulfhydryl Compounds / metabolism

Substances

  • Arsenicals
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • Oxides
  • Recombinant Fusion Proteins
  • Sulfhydryl Compounds
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • Arsenic Trioxide