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However, its mechanism is still unclear. Herein, we found that of nine common protein kinases C (PKCs), PKC\u2010\u03b2 overexpression was significantly related with TKI resistance. Blockage of its expression in CD34+ cells and CML cell lines increased sensitivity to imatinib. Then, eighty\u2010four leukemia related genes were compared between TKI\u2010resistant CML cell lines with PKC\u2010\u03b2 silenced or not. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that Arachidonate 5\u2010lipoxygenase (Alox5) and its relative pathway mainly participated in the resistance induced by PKC\u2010\u03b2 overexpression. It's also observed that Alox5 was increased not only in bone marrow biopsy but also in CD34\n                    <jats:sup>+<\/jats:sup>\n                    cells derived from IM\u2010resistant CML patients. The signaling pathway exploration indicated that ERK1\/2 pathway mediates Alox5 upregulation by PKC\u2010\u03b2. Meanwhile, we also proved that Alox5 induces TKI\u2010insensitivity in CML through inactivation of PTEN. In vivo experiment, PKC\u2010\u03b2 elective inhibitor LY333531 prolonged survival time in CML\u2010PDX mice model. In conclusion, targeted on PKC\u2010\u03b2 overexpression might be a novel therapy mechanism to overcome TKI\u2010resistance in CML.\n                  <\/jats:p>","DOI":"10.1002\/jcp.30301","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T18:35:29Z","timestamp":1612982129000},"page":"6312-6327","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["PKC\u2010\u03b2\/Alox5 axis activation promotes Bcr\u2010Abl\u2010independent TKI\u2010resistance in chronic myeloid leukemia"],"prefix":"10.1002","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9220-7898","authenticated-orcid":false,"given":"Dan","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Hematology, Key Laboratory of Hematological Disease Diagnostic &amp; Treat Center of Guizhou Province Affiliated Hospital of Guizhou Medical University  Guiyang China"},{"name":"Guizhou Province Institute of 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