{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:47:02Z","timestamp":1785304022312,"version":"3.55.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":25,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874294"],"award-info":[{"award-number":["81874294"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taishan Scholars Program","award":["TSQN201812015"],"award-info":[{"award-number":["TSQN201812015"]}]},{"name":"Multidisciplinary Research and Innovation Team of Young Scholars of Shandong University","award":["2020QNQT007"],"award-info":[{"award-number":["2020QNQT007"]}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022LSW027"],"award-info":[{"award-number":["ZR2022LSW027"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Ministry of Education of China","award":["IRT_17R68"],"award-info":[{"award-number":["IRT_17R68"]}]},{"name":"State Key Laboratory of Microbial Technology","award":["WZCX2021-03"],"award-info":[{"award-number":["WZCX2021-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chronic myeloid leukemia (CML) is a hematopoietic malignancy driven by the fusion gene BCR::ABL1. Drug resistance to tyrosine kinase inhibitors (TKIs), due to BCR::ABL1 mutations and residual leukemia stem cells (LSCs), remains a major challenge in CML treatment. Here, we revealed the requirement of the vitamin D receptor (VDR) in the progression of CML. VDR was upregulated by BCR::ABL1 and highly expressed in CML cells. Interestingly, VDR knockdown inhibited the proliferation of CML cells driven by both BCR::ABL1 and TKI-resistant BCR::ABL1 mutations. Mechanistically, VDR transcriptionally regulated DDIT4 expression; reduced DDIT4 levels upon VDR knockdown triggered DNA damage and senescence via p53 signaling activation in CML cells. Furthermore, VDR deficiency not only suppressed tumor burden and progression in primary CML mice but also reduced the self-renewal capacity of CML-LSCs. Together, our study demonstrated that targeting VDR is a promising strategy to overcome TKI resistance and eradicate LSCs in CML.<\/jats:p>","DOI":"10.1093\/jmcb\/mjad066","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T07:21:00Z","timestamp":1698304860000},"source":"Crossref","is-referenced-by-count":7,"title":["Loss of the vitamin D receptor triggers senescence in chronic myeloid leukemia via DDIT4-mediated DNA damage"],"prefix":"10.1093","volume":"15","author":[{"given":"Yan","family":"Xu","sequence":"first","affiliation":[{"name":"Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Qi","sequence":"additional","affiliation":[{"name":"Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengzu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8969-6195","authenticated-orcid":false,"given":"Zhiyuan","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences , Jinan 250012 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Hematology, Heze Municipal Hospital , Heze 274031 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8522-4764","authenticated-orcid":false,"given":"Baobing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"},{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University , Jinan 250012 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,25]]},"reference":[{"key":"2024062808353176500_bib1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.cell.2011.03.035","article-title":"Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression","volume":"145","author":"Brady","year":"2011","journal-title":"Cell"},{"key":"2024062808353176500_bib2","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.ccell.2020.03.006","article-title":"Response and resistance to BCR-ABL1-targeted therapies","volume":"37","author":"Braun","year":"2020","journal-title":"Cancer Cell"},{"key":"2024062808353176500_bib3","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1101\/gad.1256804","article-title":"Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1\/TSC2 tumor suppressor 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