ORP4L is a prerequisite for the induction of T-cell leukemogenesis associated with human T-cell leukemia virus 1

Wenbin Zhong, Xiuye Cao, Guoping Pan, Qun Niu, Xiaoqin Feng, Mengyang Xu, Mingchuan Li, Yu Huang, Qing Yi, Daoguang Yan

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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 PI3Kδ to promote PI(3,4,5)P3 generation, contributing to AKT hyperactivation; NF-κB–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.

Original languageEnglish (US)
Pages (from-to)1052-1065
Number of pages14
Issue number7
StatePublished - Feb 17 2022


  • Animals
  • Apoptosis
  • Carcinogenesis/immunology
  • Cell Proliferation
  • Gene Expression Regulation, Leukemic
  • Gene Products, tax
  • HTLV-I Infections/complications
  • Human T-lymphotropic virus 1/isolation & purification
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell/genetics
  • Mice
  • Prognosis
  • Receptors, Steroid/genetics
  • T-Lymphocytes/immunology
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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