Viral-driven oncogenesis in T/NK-cell lymphomas: parallels and divergences between HTLV-1 and EBV

Int J Hematol. 2026 Apr;123(4):476-486. doi: 10.1007/s12185-025-04156-0. Epub 2026 Jan 7.

Abstract

Viruses induce approximately 12% of human cancers, including lymphomas. In the case of T/NK cell neoplasms, human T-cell leukemia virus type I (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL), and Epstein-Barr virus (EBV) is associated with extranodal NK/T-cell lymphoma (ENKTCL) and chronic active Epstein-Barr virus disease (CAEBV). Common mechanisms for lymphoma development have been proposed. Viral genes, such as tax and HTLV-1 bZIP factor (HBZ) of HTLV-1, and latent membrane protein 1 (LMP1) and BamHI A rightward transcript microRNA (miRNA-BART) of EBV, contribute to host immune evasion and modulation of host signaling pathways, resulting in the persistence of viral-infected cells. This viral strategy is closely associated with oncogenesis. Furthermore, the long-term survival of infected cells leads to the accumulation of somatic mutations and aberrant epigenetic alterations. These events eventually lead to ATL, ENKTCL, and the lymphoma-like subset of CAEBV. Interrupting these common oncogenic mechanisms is a promising therapeutic strategy for viral-driven lymphomas with poor prognoses.

Keywords: Adult T-cell leukemia-lymphoma; Chronic active Epstein–Barr virus disease; Epstein–Barr virus; Extranodal NK/T-cell lymphoma; Human T-cell leukemia virus type I.

Publication types

  • Review

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Carcinogenesis* / genetics
  • Epigenesis, Genetic
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / virology
  • HTLV-I Infections / complications
  • Herpesvirus 4, Human* / genetics
  • Herpesvirus 4, Human* / pathogenicity
  • Human T-lymphotropic virus 1* / genetics
  • Human T-lymphotropic virus 1* / pathogenicity
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell* / genetics
  • Leukemia-Lymphoma, Adult T-Cell* / virology
  • Lymphoma, Extranodal NK-T-Cell* / etiology
  • Lymphoma, Extranodal NK-T-Cell* / genetics
  • Lymphoma, Extranodal NK-T-Cell* / virology

Substances

  • Basic-Leucine Zipper Transcription Factors