{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:50:19Z","timestamp":1791528619489,"version":"4.3.4"},"reference-count":50,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>\n                    Nonviral gene therapy with specific short interfering RNAs (siRNAs) against\n                    <jats:italic toggle=\"yes\">BCR-Abl<\/jats:italic>\n                    can be an alternative and\/or supportive therapy of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs), given the often observed resistance to TKIs in clinical setting. In this study, we explored the feasibility of BCR-Abl siRNA therapy in CML K562 cells in vitro by employing a cationic polymer derived from cholesterol (Chol) grafted low-molecular weight polyethyleneimine (PEI). The first generation TKI imatinib upregulated the expression of\n                    <jats:italic toggle=\"yes\">BCR-Abl<\/jats:italic>\n                    in K562 cells as expected. Delivery of BCR-Abl siRNA in both drug-sensitive and drug-resistant K562 cells significantly downregulated the mRNA levels in both cell types. Similarly, the\n                    <jats:italic toggle=\"yes\">BCR-Abl<\/jats:italic>\n                    siRNA treatment arrested the growth of both drug-sensitive and drug-resistant K562 cells with no obvious differences despite a large difference in drug responsiveness. The\n                    <jats:italic toggle=\"yes\">BCR-Abl<\/jats:italic>\n                    gene silencing in combination with TKI treatments exhibited significant synergism in drug-resistant K562 cells in generating substantial antileukemic activity, where the TKIs on their own were not effective. The effect of BCR-Abl siRNA and TKIs on non-CML cells (Jurkat and primary fibroblast) was negligible, indicating the specificity of the proposed therapy. This strategy can significantly overcome TKI resistance in CML cells, suggesting a feasible and effective treatment model for CML patients suffering from clinical resistances.\n                  <\/jats:p>","DOI":"10.1089\/scd.2018.0196","type":"journal-article","created":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T08:50:02Z","timestamp":1545814202000},"page":"734-744","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["<i>BCR-Abl<\/i>\n                    Silencing by siRNA: A Potent Approach to Sensitize Chronic Myeloid Leukemia Cells to Tyrosine Kinase Inhibitor Therapy"],"prefix":"10.1177","volume":"28","author":[{"given":"Remant","family":"KC","sequence":"first","affiliation":[{"name":"Department of Chemical &amp; Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bindu","family":"Thapa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anyeld","family":"Ubeda","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Medicine, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Uluda\u011f","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; 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