Authors: Coe, Emma¹; Schimmer, Aaron²

Source: Leukemia and Lymphoma, Volume 49, Number 10, October 2008 , pp. 1976-1981(6)

Publisher: Informa Healthcare

Abstract:

Arsenic trioxide (As2O3) is currently employed as a treatment for relapsed acute promyelocytic leukemia (APL), where it can induce remission in greater than 90% of patients, but is ineffective in patients with non-APL acute myeloid leukemia (AML). As2O3 induces apoptosis in APL cells through mechanisms dependent and independent of the PML-RARα fusion protein. Through PML-RARα fusion-independent mechanisms, As2O3 increases H2O2 production via its effects on glutathione and glutathione peroxidase. Catalase is an alternative mechanism to convert H2O2 to water. Therefore, we explored the relationship between catalase activity and As2O3 sensitivity. In AML and APL cell lines, but not primary patient samples, basal catalase levels matched sensitivity to As2O3. However, the chemical inhibition of catalase did not enhance As2O3-induced cell death. Failure of catalase inhibition to sensitise cells to As2O3 was due to a failure of catalase inhibition to increased levels of reactive oxygen species. Therefore, other strategies should be explored to enhance the cytotoxicity of As2O3 in AML.

Keywords: Chemotherapeutic approaches; neoplasia; myeloid leukemias; dysplasia; pharmacotherapeutics

Document Type: Research article

DOI: http://dx.doi.org/10.1080/10428190802353617

Affiliations: 1: Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada,Department of Medical Biophysics, University of Toronto, Canada 2: Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada,Department of Medical Biophysics, University of Toronto, Canada,Department of Medicine, University of Toronto, Canada

Publication date: 2008-10-01

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