Catalase activity and arsenic sensitivity in acute leukemia.

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-RARalpha fusion protein. Through PML-RARalpha 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.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Coe E,Schimmer AD

doi

10.1080/10428190802353617

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

1976-81

issue

10

eissn

1042-8194

issn

1029-2403

pii

904755694

journal_volume

49

pub_type

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