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Here, we show that aberrant overexpression of the <jats:italic>Ellis Van Creveld<\/jats:italic> (<jats:styled-content style=\"fixed-case\">EVC<\/jats:styled-content>) family is responsible for cellular Hedgehog (<jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content>) activation, which provides the pro\u2010survival ability of <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> cells. Using microarray, quantitative <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and immunohistochemistry we have demonstrated that <jats:styled-content style=\"fixed-case\">EVC<\/jats:styled-content> is significantly upregulated in <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> and human T\u2010cell leukemia virus type I (<jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101)\u2010infected cells. Epigenetic marks, including histone H3 acetylation and Lys4 trimethylation, are specifically accumulated at the <jats:italic><jats:styled-content style=\"fixed-case\">EVC<\/jats:styled-content><\/jats:italic> locus in <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> samples. The <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 Tax participates in the coordination of <jats:styled-content style=\"fixed-case\">EVC<\/jats:styled-content> expression in an epigenetic fashion. The treatment of sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> targeting <jats:styled-content style=\"fixed-case\">EVC<\/jats:styled-content>, as well as the transcription factors for <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> signaling, diminishes the <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> activation and leads to apoptotic death in <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> cell lines. We also showed that a <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> signaling inhibitor, <jats:styled-content style=\"fixed-case\">GANT<\/jats:styled-content>61, induces strong apoptosis in the established <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> cell lines and patient\u2010derived primary <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> cells. Therefore, our data indicate that <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> activation is involved in the regulation of leukemic cell survival. The epigenetically deregulated <jats:styled-content style=\"fixed-case\">EVC<\/jats:styled-content> appears to play an important role for <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> activation. The possible use of <jats:styled-content style=\"fixed-case\">EVC<\/jats:styled-content> as a specific cell marker and a novel drug target for <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101\u2010infected T\u2010cells is implicated by these findings. The <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> inhibitors are suggested as drug candidates for <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> therapy. Our findings also suggest chromatin rearrangement associated with active histone markers in <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cas.12480","type":"journal-article","created":{"date-parts":[[2014,7,4]],"date-time":"2014-07-04T07:32:53Z","timestamp":1404459173000},"page":"1160-1169","source":"Crossref","is-referenced-by-count":18,"title":["Epigenetic deregulation of <i>Ellis Van Creveld<\/i> confers robust Hedgehog signaling in adult T\u2010cell leukemia"],"prefix":"10.1111","volume":"105","author":[{"given":"Ryutaro","family":"Takahashi","sequence":"first","affiliation":[{"name":"Graduate School of Frontier Sciences The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Graduate School of Frontier Sciences The University of Tokyo Tokyo 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