Abstract 1848: Let-7 brings new insights into chronic myeloid leukemia therapy.

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/translational level. Up to date, there are approximately 2,000 human miRNA transcripts have been characterized, which are estimated to modulate more than 30% human genes and are widely involved in many essential biological processes including differentiation, proliferation, apoptosis, and also tumorigenesis. In this study, we studied let-7, a miRNA with tumor suppressive signature, for its therapeutic potential in CML. When treating CML K562 and KU812 cell by imatinib, let-7 can be significantly induced. Overexpression of let-7 can sensitize K562 and KU812 cells to imatinib, while knock-down of let-7 can increase the drug resistance of these cells. The mechanistic studies found that let-7 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-7 is a potential target for treating CML by imatinib and/or other anti-cancer druges. The pro-apoptosis and anti-proliferation roles of let-7 in CML cells may provide novel insights into discovery and development novel drugs for conquering this malignant disease. Citation Format: Bin Yi, Xiaobo Li, Wenjun Du, Gary A. Piazza, Yaguang Xi. Let-7 brings new insights into chronic myeloid leukemia therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1848. doi:10.1158/1538-7445.AM2013-1848 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.