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We analysed 48 patients with BCR::ABL1\u2010independent resistance for the presence of secondary fusion genes by RNA sequencing. We identified 10 of the most frequently detected secondary fusions in 21 patients. Validation studies, cell line models, gene expression analysis and drug screening revealed differences with respect to proliferation rate, differentiation and drug sensitivity. Notably, expression of RUNX1::MECOM led to resistance to ABL1 tyrosine kinase inhibitors in vitro. These results suggest secondary fusions contribute to BCR::ABL1\u2010independent resistance and may be amenable to combined therapies.<\/jats:p>","DOI":"10.1111\/bjh.18515","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T12:06:35Z","timestamp":1666267595000},"page":"323-328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Secondary fusion proteins as a mechanism of <scp>BCR<\/scp>::<scp>ABL1<\/scp> kinase\u2010independent resistance in chronic myeloid leukaemia"],"prefix":"10.1111","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7702-4172","authenticated-orcid":false,"given":"Evan J.","family":"Barnes","sequence":"first","affiliation":[{"name":"Division of Hematology and Medical Oncology Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Eide","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Kaempf","sequence":"additional","affiliation":[{"name":"Biostatistics Shared Resource Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bottomly","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle A.","family":"Romine","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Wilmot","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology Knight Cancer Institute, Oregon Health &amp; 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