Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug-resistant trait by delivering miR-365 |
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Authors: | Qing-Hua Min Xiao-Zhong Wang Jing Zhang Qing-Gen Chen Shu-Qi Li Xiao-Qing Liu Jing Li Jing Liu Wei-Ming Yang Yu-Huan Jiang Yan-Mei Xu Jin Lin Qiu-Fang Gao Fan Sun Lei Zhang Bo Huang |
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Institution: | 1. Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, No.1 Min De Road, Nanchang, China;2. The Medical School of Nanchang University, Nanchang, China;3. Departments of Clinical Laboratory, the First Affiliated Hospital of Nanchang University, Nanchang, China |
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Abstract: | Chronic myeloid leukemia (CML) is a malignant disorder of hematopoietic stem/progenitor cells. Majority of patients can be effectively treated with tyrosine kinase inhibitors (TKIs) such as imatinib, but a portion of patients will develop drug resistance. Accumulated evidences have identified exosomes in cancer as promoters of tumor progression. Herein, we found that exosomes derived from imatinib resistant CML cells can be internalized into sensitive CML cells and confer drug-resistance traits. We also demonstrated a significant higher level of miR-365 in exosomes derived from drug-resistant CML cells compared with those from sensitive ones using microarray and qRT-PCR. The imatinib sensitive CML cells transfected with pre-miR-365 displayed lower chemosensitivity and apoptosis rate compared with controls. We further confirmed that exosomal transfer of miR-365 induced drug resistance by inhibiting expression of pro-apoptosis protein in sensitive CML cells. In conclusion, our study reveals that exosomes mediate a horizontal transfer of drug-resistant trait in chronic myeloid leukemia cell by delivering miR-365. |
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Keywords: | Chronic myeloid leukemia Exosomes Chemosensitivity MiR-365 |
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