Abstract
Abstract Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease (MPD) that comprises 15-20% of human hemapoietic cancers. Exciting advances in molecular mechanism-based strategies have yielded imatinib mesylate/STI571/Gleevec, which has proven to be effective in many human patients with CML. Unfortunately, Gleevec is not effective in some human CML patients, whereas some CML patients become refractory to Gleevec due to the development of drug resistance caused by mutations in abl. Furthermore, Gleevec becomes significantly less effective if the CML evolves to blast crisis. Therefore, elucidating the molecular mechanisms underlying CML pathogenesis is of significance for the development of more effective molecular target-based therapy for CML patients. In this study, we demonstrated that the IRF8 expressed is decreased in human CML/AML cells and the IRF8 promoter is methylated in human CML/AML cells and in PMBC derived from human CML patients. Ectopic expression of IRF8 in myeloid cells suppressed tumor development in mice in vivo. We further demonstrated that IRF8 regulates Fas and FLIP expression in myeloid leukemia cells to mediated Fas-mediated apoptosis. Taken together, our data suggest that myeloid leukemia cells use DNA methylation to silence IRF8 expression to acquire a Fas-resistant phenotype to escape from cancer immunosurveillance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-7.
Published Version
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