{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:17:19Z","timestamp":1779167839799,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007655","name":"Aichi Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["19cm0106301h0004"],"award-info":[{"award-number":["19cm0106301h0004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20cm0106301h0005"],"award-info":[{"award-number":["20cm0106301h0005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Multiple oncogenic events are involved in the development of adult T\u2010cell leukaemia\/lymphoma (ATL). Because CD28 plays a pivotal role in T\u2010cell activation, we focused on alterations of the <jats:italic>CD28<\/jats:italic> gene in ATL. We found multiple genetic abnormalities related to <jats:italic>CD28<\/jats:italic> among the 144 patients enrolled in the present study. These involved gene fusions with the <jats:italic>cytotoxic T\u2010lymphocyte\u2010associated antigen 4<\/jats:italic> or the <jats:italic>inducible T\u2010cell co\u2010stimulator<\/jats:italic> in 14 patients (10%), <jats:italic>CD28<\/jats:italic>\u2010activating mutations in 3 (2%), and <jats:italic>CD28<\/jats:italic> copy number variations in 34 (24%). Patients with such <jats:italic>CD28<\/jats:italic> gene alterations were significantly younger than those without. In patients not receiving allogeneic haematopoietic stem cell transplantation, those with <jats:italic>CD28<\/jats:italic> gene alterations tended to have a worse prognosis than those without. Finally, patients with chronic or smouldering ATL subtypes with <jats:italic>CD28<\/jats:italic> gene alterations had a significantly worse prognosis than those without. These findings indicate that ATL, especially chronic or smouldering subtypes, have a more aggressive clinical course and are more refractory to conventional chemotherapies or mogamulizumab if they harbour <jats:italic>CD28<\/jats:italic> gene alterations, likely because of continuous, prolonged, and enhanced CD28 activatory signalling. Novel treatment strategies to overcome the effects of these <jats:italic>CD28<\/jats:italic> gene alterations are warranted.<\/jats:p>","DOI":"10.1111\/bjh.17211","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T15:43:03Z","timestamp":1605714183000},"page":"281-291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Clinical significance of <i>CD28<\/i> gene\u2010related activating alterations in adult T\u2010cell leukaemia\/lymphoma"],"prefix":"10.1111","volume":"192","author":[{"given":"Yuma","family":"Sakamoto","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Graduate School of Medical Sciences Nagoya City University Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1060-0777","authenticated-orcid":false,"given":"Takashi","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Immunology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Graduate School of Medical Sciences Nagoya City University Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morishige","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine Fukuoka University Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Kyushu Medical Center Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Yonekura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Imamura General Hospital Kagoshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukie","family":"Tashiro","sequence":"additional","affiliation":[{"name":"Department of Pathology Imamura General Hospital Kagoshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asahi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Graduate School of Medical Sciences Nagoya City University Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Kusumoto","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Graduate School of Medical Sciences Nagoya City University Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atae","family":"Utsunomiya","sequence":"additional","affiliation":[{"name":"Department of Hematology Imamura General Hospital Kagoshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsuke","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Graduate School of Medical Sciences Nagoya City University Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuzo","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Tumor Immunology School of Medicine Aichi Medical University Nagakute Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6157-636X","authenticated-orcid":false,"given":"Hiroshi","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Graduate School of Medical Sciences Nagoya City University Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V50.3.481.481"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1991.tb08051.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2111"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70202-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3415"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3405"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.04.020"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa8172"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3370"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.186767"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3444"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0473-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02737.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.9958"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00501"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-414490"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2013.09.014"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02235"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-2697"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.3472"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13338"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.7732"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64012-6"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.126"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-02-835991"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2010.11.022"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190600687547"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(96)00075-X"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.357"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2017.07.002"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3356"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-02-698977"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001815"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.17211","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.17211","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.17211","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T17:20:15Z","timestamp":1693416015000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.17211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,18]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1111\/bjh.17211"],"URL":"https:\/\/doi.org\/10.1111\/bjh.17211","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,18]]},"assertion":[{"value":"2020-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}