Abstract 1742: Suppression of Akt activity selectively induced apoptosis of Ara-C resistant AML cells

Abstract

Abstract Treatment outcome of acute myeloid leukemia (AML), intensive Ara-C chemotherapy, remains unsatisfactory. It has been shown that the frequency of relapse is high and only 20 to 30% rate of the overall five year survival. Ara-C resistance could be one of major factors in decreasing the efficacy of intensive Ara-C chemotherapy. In this study, we established in vitro Ara-C resistant AML cell lines (KG1 and ML-1) and examined to ascertain the cause of Ara-C resistance. The expression levels of CDA in Ara-C resistant cell lines were higher than in parental cell line. However, the expression of other genes was not significantly different. Besides, PI3K/AKT was persistantly activated in Ara-C resistant cell lines. Also, mTOR, downstream of AKT, was highly expressed in AML resistant cell lines. MTT assay showed that PI3K specific inhbitor, LY29002, and mTOR inhibitor, rapamycin, inhibited the growth of AML cells and there was no different among AML cells. A synergic effect of Ara-C induced apoptosis was not detected in AML cells co-treated with rapamycin. Nevertheless, LY29002 and rapamycin was more effective to induce apoptosis in Ara-C resistant AML cell lines. Our data indicated that persistent activation of Akt in AML cells contributed to becoming resistant to Arc-C treatments. Inhibition of Akt activation would be a potential target to overcome Ara-C resistance in AML. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1742. doi:10.1158/1538-7445.AM2011-1742