| First Author | Zhong W | Year | 2022 |
| Journal | Blood | Volume | 139 |
| Issue | 7 | Pages | 1052-1065 |
| PubMed ID | 34797912 | Mgi Jnum | J:322742 |
| Mgi Id | MGI:7260066 | Doi | 10.1182/blood.2021013579 |
| Citation | Zhong W, et al. (2022) ORP4L is a prerequisite for the induction of T-cell leukemogenesis associated with human T-cell leukemia virus 1. Blood 139(7):1052-1065 |
| abstractText | 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 PI3Kdelta to promote PI(3,4,5)P3 generation, contributing to AKT hyperactivation; NF-kappaB-dependent, 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. |
