Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug-resistant trait by delivering miR-365
- Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, No.1 Min De Road, Nanchang (China)
Highlights: • Imatinib resistant CML cells-derived exosomes are internalized into sensitive CML cells. • Imatinib resistant CML cells-derived exosomes confer drug resistance trait to sensitive CML cells. • Exosomes mediate horizontal transfer of miR-365 between imatinib resistant CML cells and sensitive ones. • MiR-365 lowers chemosensitivity and apoptosis in imatinib-sensitive CML cells. 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.
- OSTI ID:
- 23082491
- Journal Information:
- Experimental Cell Research, Vol. 362, Issue 2; Other Information: Copyright (c) 2017 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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