Adult T‐cell leukemia cells are characterized by abnormalities of Helios expression that promote T cell growth. Issue 8 (19th May 2013)

• Record Type: Journal Article
• Authors: Asanuma, Satomi; Yamagishi, Makoto; Kawanami, Katsuaki; Nakano, Kazumi; Sato‐Otsubo, Aiko; Muto, Satsuki; Sanada, Masashi; Yamochi, Tadanori; Kobayashi, Seiichiro; Utsunomiya, Atae; Iwanaga, Masako; Yamaguchi, Kazunari; Uchimaru, Kaoru; Ogawa, Seishi; Watanabe, Toshiki
• Is Part Of: Cancer science. Volume 104:Issue 8(2013:Aug.)
• Page Start: 1097
• Page End: 1106
• Publication Date: 2013-05-19
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.12181
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : Molecular abnormalities involved in the multistep leukemogenesis of adult T‐cell leukemia (ATL) remain to be clarified. Based on our integrated database, we focused on the expression patterns and levels of Ikaros family genes, Ikaros, Helios, and Aiolos, in ATL patients and HTLV‐1 carriers. The results revealed profound deregulation of Helios expression, a pivotal regulator in the control of T‐cell differentiation and activation. The majority of ATL samples (32/37 cases) showed abnormal splicing of Helios expression, and four cases did not express Helios. In addition, novel genomic loss in Helios locus was observed in 17/168 cases. We identified four ATL‐specific short Helios isoforms and revealed their dominant‐negative function. Ectopic expression of ATL‐type Helios isoform as well as knockdown of normal Helios or Ikaros promoted T‐cell growth. Global mRNA profiling and pathway analysis showed activation of several signaling pathways important for lymphocyte proliferation and survival. These data provide new insights into the molecular involvement of Helios function in the leukemogenesis and phenotype of ATL cells, indicating that Helios deregulation is one of the novel molecular hallmarks of ATL.