{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:42:49Z","timestamp":1790797369898,"version":"4.1.0"},"reference-count":43,"publisher":"American Society of Hematology","issue":"7","license":[{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human T-cell leukemia virus 1 (HTLV-1) causes adult T-cell leukemia (ATL), but the mechanism underlying its initiation remains elusive. In this study, ORP4L was expressed in ATL cells but not in normal T-cells. ORP4L ablation completely blocked T-cell leukemogenesis induced by the HTLV-1 oncoprotein Tax in mice, whereas engineering ORP4L expression in T-cells resulted in T-cell leukemia in mice, suggesting the oncogenic properties and prerequisite of ORP4L promote the initiation of T-cell leukemogenesis. For molecular insight, we found that loss of miR-31 caused by HTLV-1 induced ORP4L expression in T-cells. ORP4L interacts with PI3K\u03b4 to promote PI(3,4,5)P3 generation, contributing to AKT hyperactivation; NF-\u03baB\u2013dependent, p53 inactivation-induced pro-oncogene expression; and T-cell leukemogenesis. Consistently, ORP4L ablation eliminates human ATL cells in patient-derived xenograft ATL models. These results reveal a plausible mechanism of T-cell deterioration by HTLV-1 that can be therapeutically targeted.<\/jats:p>","DOI":"10.1182\/blood.2021013579","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T18:01:32Z","timestamp":1637344892000},"page":"1052-1065","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":10,"title":["ORP4L is a prerequisite for the induction of T-cell leukemogenesis associated with human T-cell leukemia virus 1"],"prefix":"10.1182","volume":"139","author":[{"given":"Wenbin","family":"Zhong","sequence":"first","affiliation":[{"name":"Ministry of Education (MOE) Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5015-0160","authenticated-orcid":false,"given":"Xiuye","family":"Cao","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3704-6649","authenticated-orcid":false,"given":"Guoping","family":"Pan","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Niu","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Feng","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyang","family":"Xu","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5185-6392","authenticated-orcid":false,"given":"Mingchuan","family":"Li","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1277-6784","authenticated-orcid":false,"given":"Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"City University of Hong Kong, Hong Kong, China; 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