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However, some patients acquire resistance to TKI<\/jats:styled-content> that is frequently associated with point mutations in BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content>. We previously reported that a medium\u2010chain fatty\u2010acid derivative AIC<\/jats:styled-content>\u201047 induced transcriptional suppression of BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content><\/jats:italic> and perturbation of the Warburg effect, leading to growth inhibition in Ph\u2010positive leukemia cells. Herein, we showed that AIC<\/jats:styled-content>\u201047 had anti\u2010leukemic effects in either wild type (WT<\/jats:styled-content>)\u2010 or mutated\u2010BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content>\u2010harboring cells. AIC<\/jats:styled-content>\u201047 suppressed transcription of BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content><\/jats:italic> gene regardless of the mutation through downregulation of transcriptional activator, c\u2010Myc. Reprogramming of the metabolic pathway has been reported to be associated with resistance to anti\u2010cancer drugs; however, we found that a point mutation of BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content> was independent of the profile of pyruvate kinase muscle (PKM<\/jats:styled-content>) isoform expression. Even in T315I\u2010mutated cells, AIC<\/jats:styled-content>\u201047 induced switching of the expression profile of PKM<\/jats:styled-content> isoforms from PKM<\/jats:styled-content>2 to PKM<\/jats:styled-content>1, suggesting that AIC<\/jats:styled-content>\u201047 disrupted the Warburg effect. In a leukemic mouse model, AIC<\/jats:styled-content>\u201047 greatly suppressed the increase in BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content><\/jats:italic> mRNA<\/jats:styled-content> level and improved hepatosplenomegaly regardless of the BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content> mutation. Notably, the improvement of splenomegaly by AIC<\/jats:styled-content>\u201047 was remarkable and might be equal to or greater than that of TKI<\/jats:styled-content>. These findings suggest that AIC<\/jats:styled-content>\u201047 might be a promising agent for overcoming the resistance of Ph\u2010positive leukemia to therapy.<\/jats:p>","DOI":"10.1111\/cas.13913","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T11:59:05Z","timestamp":1544615945000},"page":"751-760","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Potent antiproliferative effect of fatty\u2010acid derivative AIC<\/scp>\u201047 on leukemic mice harboring BCR<\/scp>\u2010ABL<\/scp> mutation"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8326-1203","authenticated-orcid":false,"given":"Haruka","family":"Shinohara","sequence":"first","affiliation":[{"name":"United Graduate School of Drug Discovery and Medical Information Sciences Gifu University Gifu 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