{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:06:41Z","timestamp":1777374401385,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adult T\u2010cell leukemia\/lymphoma (<jats:styled-content style=\"fixed-case\">ATLL<\/jats:styled-content>) is a mature T\u2010cell neoplasm, and is divided into 2 indolent (smoldering and chronic) and 2 aggressive (acute and lymphoma) clinical subtypes. Based on previous integrated molecular analyses suggesting the importance of the JAK\u2010<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content> pathway in <jats:styled-content style=\"fixed-case\">ATLL<\/jats:styled-content>, we attempted to clarify the clinicopathological significance of this pathway. Clinical and morphological findings were reviewed in 116 cases with <jats:styled-content style=\"fixed-case\">ATLL<\/jats:styled-content>. The nuclear localizations of phosphorylated <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 (<jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>3), <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>5, and <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>6 were analyzed by immunohistochemistry. Targeted sequencing was undertaken on the portion of <jats:italic><jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3<\/jats:italic> encoding the Src homology 2 domain. Expression of <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>3 was observed in 43% (50\/116) of <jats:styled-content style=\"fixed-case\">ATLL<\/jats:styled-content> cases, whereas <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>5 and <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>6 were largely undetected. Cases with the lymphoma type showed significantly less frequent <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>3 expression (8\/45, 18%) than those with the other subtypes (41\/66, 62%; <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a0.001). <jats:italic><jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3<\/jats:italic> mutations were detected in 36% (10\/28) and 19% (12\/64) of cases with the smoldering and aggressive types of <jats:styled-content style=\"fixed-case\">ATLL<\/jats:styled-content>, respectively. The correlation between <jats:italic><jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3<\/jats:italic> mutation and <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>3 expression was not significant (<jats:italic>P\u00a0<\/jats:italic>=\u00a0.07). Both univariate and multivariate analysis revealed that <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>3 expression was significantly associated with better overall survival and progression\u2010free survival in the smoldering type of <jats:styled-content style=\"fixed-case\">ATLL<\/jats:styled-content>, whereas <jats:italic><jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3<\/jats:italic> mutation was not related to a line of clinical outcome. Collectively, our data show that only the lymphoma type showed a low prevalence of tumor cells positive for <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>3 expression, and raises the possibility that <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>3 expression is a novel biomarker to predict better prognosis in the smoldering type of ATLL.<\/jats:p>","DOI":"10.1111\/cas.14114","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T19:56:29Z","timestamp":1561492589000},"page":"2982-2991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Phosphorylated <scp>STAT<\/scp>3 expression predicts better prognosis in smoldering type of adult T\u2010cell leukemia\/lymphoma"],"prefix":"10.1111","volume":"110","author":[{"given":"Kazuho","family":"Morichika","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine) Graduate School of Medicine University of the Ryukyus Nishihara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1205-858X","authenticated-orcid":false,"given":"Kennosuke","family":"Karube","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Graduate School of Medicine University of the Ryukyus Nishihara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirona","family":"Kayo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of the Ryukyus Nishihara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuta","family":"Uchino","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of the Ryukyus Nishihara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Nishi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine) Graduate School of Medicine University of the Ryukyus Nishihara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sawako","family":"Nakachi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine) Graduate School of Medicine University of the Ryukyus Nishihara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiki","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine) Graduate School of Medicine University of the Ryukyus Nishihara 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