論文

査読有り
2017年9月

Genetic alterations in adult T-cell leukemia/lymphoma

CANCER SCIENCE
  • Yasunori Kogure
  • ,
  • Keisuke Kataoka

108
9
開始ページ
1719
終了ページ
1725
記述言語
英語
掲載種別
DOI
10.1111/cas.13303
出版者・発行元
WILEY

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm with a dismal prognosis. It is caused by human T-cell leukemia virus type-1 (HTLV-1) retrovirus. A long latency period from HTLV-1 infection to ATL onset suggests that not only HTLV-1 proteins, such as Tax and HBZ, but also additional genetic and/or epigenetic events are required for ATL development. Although many studies have demonstrated the biological functions of viral genes, alterations of cellular genes associated with ATL have not been fully investigated. Recently, a largescale integrated genetic analysis revealed the entire landscape of somatic aberrations in ATL. This neoplasm is characterized by frequent gain-of-function alterations in components of the T-cell receptor/NF-kappa B signaling pathway, including activating mutations in the PLCG1, PRKCB, CARD11 and VAV1 genes, and CTLA4-CD28 and ICOS-CD28 fusions. Importantly, molecules associated with immune surveillance, such as HLA-A/B, CD58 and FAS, are affected recurrently. Among them, one notable lesion occurs as frequent structural variations that truncate the PD-L1 3'-untranslated region, leading to its overexpression. Other genetic targets include transcription factors (IRF4, IKZF2, and GATA3) and chemokine receptors (CCR4, CCR7 and GPR183), which are functionally relevant in normal T cells. A substantial proportion of ATL cases show widespread accumulation of repressive epigenetic changes, such as trimethylation of histone H3 lysine 27 and DNA hypermethylation of CpG islands, which coordinately modulate multiple pathways, including Cys2-His2 zinc finger genes involved in silencing retroelements. Here we review the current understanding of the genetic/epigenetic aberrations in ATL, focusing on their relevance in its molecular pathogenesis.

Web of Science ® 被引用回数 : 25

リンク情報
DOI
https://doi.org/10.1111/cas.13303
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000408945300001&DestApp=WOS_CPL
URL
http://orcid.org/0000-0002-8263-9902

エクスポート
BibTeX RIS