Abstract 1456: MicroRNA improves the efficacy of imatinib on the treatment of chronic myeloid leukemia

Abstract

Abstract Human chronic myelogenous leukemia (CML) is a malignancy of pluripotent hematopoietic cells that is caused by the deregulated activity of the tyrosine kinase that is encoded by the chimeric bcr-abl oncogene. Given that CML cells are usually highly resistant to chemotherapy, novel and more efficacious strategies against this disease are urgently needed. MicroRNA (miRNA) is a set of newly discovered 20-22 nucleotides RNA molecules, and they broadly repress their cognate target genes at post-transcriptional/trans-lational level. To date, there are approximately 2,500 human miRNA transcripts have been characterized, which are estimated to modulate more than 30% human genes by being involved in many essential normal biological and pathological processes including differentiation, proliferation, apoptosis, and tumorigenesis as well. In this study, we studied let-7a, a miRNA with tumor suppressive signature, for its therapeutic potential in CML. When treating CML K562 and KU812 cell by imatinib, let-7a can be significantly induced. Overexpression of let-7a can sensitize K562 and KU812 cells to imatinib, while knock-down of let-7a can increase the resistance of these cells towards this drug. The functional studies found that let-7a was able to promote apoptosis of CML cells, inhibit the tumor cell proliferation, and lead to a cell cycle arrest in the G0/G1 phase. These results demonstrate that let-7a is a potential target for treating CML by imatinib and/or other anti-cancer drugs. The pro-apoptosis and anti-proliferation roles of let-7a in CML cells may provide novel insights into discovery and development of more efficacious drugs for treating this malignant disease. Citation Format: Bin Yi, Ruixia Ma, Xiangling Feng, Zhiwei Xing, Xiaoguo Zhang, Gary Piazza, Yaguang Xi. MicroRNA improves the efficacy of imatinib on the treatment of chronic myeloid leukemia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1456. doi:10.1158/1538-7445.AM2014-1456