{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:20:28Z","timestamp":1780381228156,"version":"3.54.1"},"reference-count":57,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A2C2002177"],"award-info":[{"award-number":["NRF-2019R1A2C2002177"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Previous studies have suggested that statins can be repurposed for cancer treatment. However, the therapeutic efficacy of statins in chronic myeloid leukemia (CML) has not yet been demonstrated. In this study, we retrospectively evaluated the outcomes of 408 CML patients who underwent imatinib therapy. The deep molecular response rates in patients treated with the statin\/TKI combination were significantly higher than those in patients treated with TKI alone (p = 0.0016). The statin\/TKI combination exerted potent cytotoxic effects against wild-type and ABL1 mutant CML, BaF3, and K562\/T315I mutant cells. Furthermore, the statin\/TKI combination additively inhibited the colony-forming capacity of murine CML-KLS+ cells in vitro. In addition, we examined the additive growth-inhibitory effects of the statin\/tyrosine kinase inhibitor (TKI) combination against CML patient-derived CD34+ cells. The growth-inhibitory effects of the statin\/imatinib combination against CD34+\/CML primary cells were higher than those against CD34+\/Norm cells (p = 0.005), suggesting that the combination of rosuvastatin and imatinib exerted growth-inhibitory effects against CML CD34+ cells, but not against normal CD34+ cells. Furthermore, results from RNA sequencing of control and statin-treated cells suggested that statins inhibited c-Myc-mediated and hematopoietic cell differentiation pathways. Thus, statins can be potentially repurposed to improve treatment outcomes in CML patients when combined with TKI therapy.<\/jats:p>","DOI":"10.3390\/cancers13215543","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T22:25:54Z","timestamp":1636064754000},"page":"5543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Statins Enhance the Molecular Response in Chronic Myeloid Leukemia when Combined with Tyrosine Kinase Inhibitors"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4875-6627","authenticated-orcid":false,"given":"Hyeok-Jae","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Min","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6646-6004","authenticated-orcid":false,"given":"Kazuhito","family":"Naka","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Clinical Genomics Center, Samsung Medical Center, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho-Jae","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Sook","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Chonnam National University School of Medicine, Hwasun 58128, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taehyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada"},{"name":"The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Hematology, Saga University School of Medicine, Saga 840-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Zarabi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 2M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Lipton","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 2M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Minden","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 2M9, Canada"},{"name":"Ontario Cancer Institute, University of Toronto, Toronto, ON M5G 2M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul-Won","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeoung-Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Chonnam National University School of Medicine, Hwasun 58128, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, Korea"},{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis Dong Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 2M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1056\/NEJMoa022457","article-title":"Imatinib Compared with Interferon and Low-Dose Cytarabine for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia","volume":"348","author":"Guilhot","year":"2003","journal-title":"N. 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