{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T14:39:33Z","timestamp":1781275173265,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic myeloid leukaemia (CML) is a haematological malignancy characterized by the constitutive tyrosine kinase activity of the BCR\u2010ABL1 fusion protein. Flumatinib, a second\u2010generation tyrosine kinase inhibitor, has exhibited superior clinical efficacy compared to its precursor, imatinib. However, with increased clinical use, resistance to flumatinib has emerged as a significant challenge. To investigate the mechanisms of flumatinib resistance in CML, we induced the human CML cell line K562 using a flumatinib concentration gradient method in\u00a0vitro, successfully establishing a flumatinib\u2010resistant K562\/FLM cell line. This cell line exhibited cross\u2010resistance to imatinib and doxorubicin, but remained sensitive to the antiparasitic agent ivermectin, which possesses antitumoural effects. Through cellular experimentation, we explored the resistance mechanisms, which indicated that K562\/FLM cells evade flumatinib cytotoxicity by enhancing autophagy, increasing the expression of membrane transport proteins, particularly P\u2010glycoprotein, ABCC1 and ABCC4, as well as enhancing phosphorylation of p\u2010EGFR, p\u2010ERK and p\u2010STAT3 proteins. Moreover, it was found that ivermectin effectively suppressed the expression of autophagy and transport proteins in K562\/FLM cells, reduced the activity of the aforementioned phosphoproteins, and promoted apoptotic cell death. Collectively, the increased autophagy, higher expression of drug\u2010efflux proteins and hyperactivation of the EGFR\/ERK\/STAT3 signalling pathway were identified as pivotal elements promoting resistance to flumatinib. The significant effects of ivermectin might offer a novel therapeutic strategy to overcome flumatinib resistance and optimize the treatment outcomes of CML.<\/jats:p>","DOI":"10.1111\/jcmm.18539","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T10:24:57Z","timestamp":1721816697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Overcoming flumatinib resistance in chronic myeloid leukaemia: Insights into cellular mechanisms and ivermectin's therapeutic potential"],"prefix":"10.1111","volume":"28","author":[{"given":"Jixian","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Hematology Yuebei People's Hospital Affiliated to Medical College of Shantou University  Shaoguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xiao","sequence":"additional","affiliation":[{"name":"Physical Examination Center Yuebei People's 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