1. Silencing of miR-21 sensitizes CML CD34+ stem/progenitor cells to imatinib-induced apoptosis by blocking PI3K/AKT pathway.
- Author
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Wang, Wei-Zhang, Pu, Qiao-Hong, Lin, Xiang-Hua, Liu, Man-Yu, Wu, Li-Rong, Wu, Qing-Qing, Chen, Yong-Heng, Liao, Fen-Fang, Zhu, Jia-Yong, and Jin, Xiao-Bao
- Subjects
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LEUKEMIA treatment , *IMATINIB , *DRUG therapy , *GENE silencing , *MICRORNA , *APOPTOSIS , *PROTEIN-tyrosine kinase inhibitors , *PROGENITOR cells - Abstract
BCR-ABL tyrosine kinase inhibitor imatinib fails to eradicate leukemia stem cells (LSCs), the underlying mechanisms maintaining CML LSCs remain poorly understood. Here, we showed that transient inhibition of miR-21 by antagomiR-21 markedly increased imatinib-induced apoptosis in CML, but not normal CD34 + stem/progenitor cells. Furthermore, PI3K inhibitors also significantly sensitized CML CD34 + cells to imatinib-induced apoptosis. MiR-21 or PI3K inhibitor in combination with imatinib treatment significantly decreased AKT phosphorylation and c-Myc expression than either agent did alone, but did not affect Bim and Bcl-6 expresssion. These findings indicate that miR-21 is required for maintaining the imatinib-resistant phenotype of CML CD34 + cells through PI3K/AKT signaling pathway, thus providing the basis for a promising therapeutic approach to eliminate CML LSCs. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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