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Previous studies have demonstrated that telomerase activity is associated with deregulated self\u2010renewal of leukemia stem cells (LSCs). Here, we identified a novel compound IX, an imatinib derivative with a replacement fragment of a telomerase inhibitor, which can effectively eradicate LSCs but had no influence on normal hematopoietic stem cells (HSCs) survival. We showed that compound IX can decrease the viability of drug\u2010resistant K562\/G cells and blast crisis CML primary patient cells. Besides, IX can affect LSC survival, inhibit the colony\u2010forming ability, and reduce LSC frequency. In vivo results showed that IX can relieve the tumor burden in patient\u2010derived xenograft (PDX) model and prolong the lifespan. We observed that compound IX can not only decrease telomerase activity, but also affect the alternative lengthening of telomeres. In addition, IX can inhibit both the canonical and non\u2010canonical Wnt pathways. Our data suggested this novel compound IX as a promising candidate for drug\u2010resistant leukemia therapy.<\/jats:p>","DOI":"10.1096\/fj.201902651rr","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T10:37:08Z","timestamp":1595846228000},"page":"8843-8857","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A small molecule compound IX inhibits telomere and attenuates oncogenesis of drug\u2010resistant leukemia cells"],"prefix":"10.1096","volume":"34","author":[{"given":"Yinghui","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology PUMC Department of Stem Cell and Regenerative Medicine CAMS Key Laboratory of Gene Therapy for Blood Diseases National Clinical Research Center for Blood Diseases Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiali","family":"Gu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology PUMC Department of Stem Cell and Regenerative Medicine CAMS Key Laboratory of Gene Therapy for Blood Diseases National Clinical Research Center for Blood Diseases Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahui","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology PUMC Department of Stem Cell and Regenerative Medicine CAMS Key Laboratory of Gene Therapy for Blood Diseases National Clinical Research Center for Blood Diseases Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College Tianjin China"},{"name":"State Key Laboratory of Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huier","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology PUMC Department of Stem Cell and Regenerative Medicine CAMS Key Laboratory of Gene Therapy for Blood Diseases National Clinical Research Center for Blood Diseases Institute of Hematology &amp; 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