{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:14:43Z","timestamp":1791141283097,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,5,19]],"date-time":"2013-05-19T00:00:00Z","timestamp":1368921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:p>Molecular abnormalities involved in the multistep leukemogenesis of adult T\u2010cell leukemia (<jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>) remain to be clarified. Based on our integrated database, we focused on the expression patterns and levels of Ikaros family genes, <jats:styled-content style=\"fixed-case\"><jats:italic>Ikaros<\/jats:italic><\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> <jats:italic>Helios<\/jats:italic><\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\"><jats:italic>Aiolos<\/jats:italic><\/jats:styled-content>, in <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> patients and <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 carriers. The results revealed profound deregulation of Helios expression, a pivotal regulator in the control of T\u2010cell differentiation and activation. The majority of <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> samples (32\/37 cases) showed abnormal splicing of Helios expression, and four cases did not express Helios. In addition, novel genomic loss in <jats:styled-content style=\"fixed-case\"><jats:italic>Helios<\/jats:italic><\/jats:styled-content> locus was observed in 17\/168 cases. We identified four <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>\u2010specific short Helios isoforms and revealed their dominant\u2010negative function. Ectopic expression of <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>\u2010type Helios isoform as well as knockdown of normal Helios or Ikaros promoted T\u2010cell growth. Global <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> 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 <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> cells, indicating that Helios deregulation is one of the novel molecular hallmarks of <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cas.12181","type":"journal-article","created":{"date-parts":[[2013,4,18]],"date-time":"2013-04-18T16:29:44Z","timestamp":1366302584000},"page":"1097-1106","source":"Crossref","is-referenced-by-count":32,"title":["Adult T\u2010cell leukemia cells are characterized by abnormalities of <scp><i>Helios<\/i><\/scp> expression that promote T cell growth"],"prefix":"10.1111","volume":"104","author":[{"given":"Satomi","family":"Asanuma","sequence":"first","affiliation":[{"name":"Graduate School of Frontier Sciences The University of Tokyo Tokyo 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