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The gate-keeper mutation T315I is the most challenging mutant due to its resistance to most tyrosine kinase inhibitors (TKIs). The third generation TKI ponatinib is the only effective TKI to treat CML patients harboring T315I-BCR-ABL mutation, but with high rate of major arterial thrombotic events. Alternative strategies to specifically target T315I-BCR-ABL are needed for the treatment of CML patients harboring such a mutation. Given that Sp1 is a fundamental transcriptional factor to positively regulate <jats:italic>WT-BCR-ABL<\/jats:italic> fusion oncogene, the purpose of this investigation was aimed at evaluating the anti-tumor activity and the underlying mechanism in terms of Sp1 regulational effect on the transcription of <jats:italic>T315I<\/jats:italic>-<jats:italic>BCR-ABL<\/jats:italic> fusion oncogene. Like in <jats:italic>WT-BCR-ABL<\/jats:italic>, we identified enrichment of Sp1 on the promoter of <jats:italic>T315I-BCR-ABL<\/jats:italic> fusion gene. Treatment of WT- and T315I-BCR-ABL-expressing CML cells by niclosamide diminished such an enrichment of Sp1, and decreased <jats:italic>WT- and T315I-BCR-ABL<\/jats:italic> transcription and its downstream signaling molecules such as STAT5 and Akt. Further, niclosamide significantly inhibited the proliferation and induced apoptosis through intrinsic pathway. The <jats:italic>in vivo<\/jats:italic> efficacy validation of <jats:italic>p<\/jats:italic>-niclosamide, a water soluble derivative of niclosamide, showed that <jats:italic>p<\/jats:italic>-niclosamide significantly inhibited the tumor burden of nude mice subcutaneously bearing T315I-BCR-ABL-expressing CML cells, and prolonged the survival of allografted leukemic mice harboring BaF3-T315I-BCR-ABL. We conclude that niclosamide is active against <jats:italic>T315I-BCR-ABL<\/jats:italic>-expressing cells, and may be a promising agent for CML patients regardless of T315I mutation status.<\/jats:p>","DOI":"10.1038\/s41419-017-0075-7","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T12:17:58Z","timestamp":1516623478000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Anthelmintic niclosamide suppresses transcription of BCR-ABL fusion oncogene via disabling Sp1 and induces apoptosis in imatinib-resistant CML cells harboring T315I mutant"],"prefix":"10.1038","volume":"9","author":[{"given":"Bei","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxuan","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,22]]},"reference":[{"key":"75_CR1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nature15248","volume":"525","author":"S Prost","year":"2015","unstructured":"Prost, S. et al. 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