{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:30:16Z","timestamp":1781116216020,"version":"3.54.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T00:00:00Z","timestamp":1580428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council of Singapore","doi-asserted-by":"crossref","award":["MOHIAFCat1-11015"],"award-info":[{"award-number":["MOHIAFCat1-11015"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council of Singapore","doi-asserted-by":"crossref","award":["NMRC-OFIRG16NOV090"],"award-info":[{"award-number":["NMRC-OFIRG16NOV090"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Pharmaceuticals, Bayer AG"},{"name":"TANOTO Foundation","award":["(NRDUKST18101)"],"award-info":[{"award-number":["(NRDUKST18101)"]}]},{"name":"LING Foundation","award":["(NRDUKSN18101)"],"award-info":[{"award-number":["(NRDUKSN18101)"]}]},{"name":"New Century Foundation","award":["(NCCRF-YR2014-SEP-SD2)"],"award-info":[{"award-number":["(NCCRF-YR2014-SEP-SD2)"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Peripheral T\u2010cell lymphomas (PTCL) and natural killer (NK)\/T\u2010cell lymphomas (NKTCL) are a heterogeneous group of aggressive malignancies with dismal outcomes and limited treatment options. While the phosphatidylinositol 3\u2010kinase (PIK3) pathway has been shown to be highly activated in many B\u2010cell lymphomas, its therapeutic relevance in PTCL and NKTCL remains unclear. The aim of this study is to investigate the expression of PIK3 and phosphatase and tensin homolog (PTEN) in these subtypes of lymphoma and to identify potential therapeutic targets for clinical testing. Therefore, the expression of PIK3\u03b1, PIK3\u03b2, PIK3\u03b3, PIK3\u03b4 and PTEN was analyzed in 88 cases of PTCL and NKTCL samples by immunohistochemistry. All PTCL and NKTCL samples demonstrated high expression of PIK3 isoforms. In particular, high PIK3\u03b1 expression was significantly associated with poor survival, even after adjustment for age, International Prognostic Index (IPI) score and anthracycline\u2010based chemotherapy in first line. Notably, copanlisib, a pan\u2010class I inhibitor with predominant activities towards PIK3\u03b1 and PIK3\u03b4 isoforms, effectively inhibited phosphorylation of AKT, 4E\u2010BP\u20101 and STAT3, causing G<jats:sub>0<\/jats:sub>\/G<jats:sub>1<\/jats:sub> cell cycle arrest and resulting in suppression of tumour cell growth <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. This study provides evidence that targeting the PIK3 pathway, particularly simultaneous inhibition of PIK3\u03b1 and \u03b4, could be a promising approach for the treatment of PTCL and NKTCL.<\/jats:p>","DOI":"10.1111\/bjh.16435","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T19:26:34Z","timestamp":1580498794000},"page":"731-744","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Evaluation of the PIK3 pathway in peripheral T\u2010cell lymphoma and NK\/T\u2010cell lymphoma"],"prefix":"10.1111","volume":"189","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7518-4081","authenticated-orcid":false,"given":"Dachuan","family":"Huang","sequence":"first","affiliation":[{"name":"Lymphoma Genomic Translational Research Laboratory Division of Cellular &amp; Molecular Research National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy Linlin","family":"Song","sequence":"additional","affiliation":[{"name":"Lymphoma Genomic Translational Research Laboratory Division of Cellular &amp; Molecular Research National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarja\u2010Liisa","family":"Nairism\u00e4gi","sequence":"additional","affiliation":[{"name":"Lymphoma Genomic Translational Research Laboratory Division of Cellular &amp; Molecular Research National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurike","family":"Laurensia","sequence":"additional","affiliation":[{"name":"Lymphoma Genomic Translational Research Laboratory Division of Cellular &amp; Molecular Research National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Lu","family":"Pang","sequence":"additional","affiliation":[{"name":"Lymphoma Genomic Translational Research Laboratory Division of Cellular &amp; Molecular Research National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl Cheah Ming","family":"Zhe","sequence":"additional","affiliation":[{"name":"Lymphoma Genomic Translational Research Laboratory Division of Cellular &amp; Molecular Research National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther Kam Yin","family":"Wong","sequence":"additional","affiliation":[{"name":"Lymphoma Genomic Translational Research Laboratory Division of Cellular &amp; Molecular Research National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovani Giovani\u2010Clarest","family":"Wijaya","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Epigenome Division of Medical Sciences National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Tan","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Epigenome Division of Medical Sciences National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3089-7379","authenticated-orcid":false,"given":"Sze Huey","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Clinical Trials and Epidemiological Sciences National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3732-8707","authenticated-orcid":false,"given":"Jing\u2010Quan","family":"Lim","sequence":"additional","affiliation":[{"name":"Lymphoma Genomic Translational Research Laboratory Division of Cellular &amp; Molecular Research National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-4871","authenticated-orcid":false,"given":"Burton Kuan Hui","family":"Chia","sequence":"additional","affiliation":[{"name":"Lymphoma Genomic Translational Research Laboratory Division of Cellular &amp; Molecular Research National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason Yongsheng","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany Pooi Ling","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagavalli","family":"Somasundaram","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology National Cancer Centre Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2140-4827","authenticated-orcid":false,"given":"Chee Leong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology Singapore General Hospital Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Politz","sequence":"additional","affiliation":[{"name":"Research &amp; Development Pharmaceuticals Bayer AG Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningshu","family":"Liu","sequence":"additional","affiliation":[{"name":"Research &amp; Development Pharmaceuticals Bayer AG Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Thye","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology National Cancer Centre Singapore Singapore City Singapore"},{"name":"Duke\u2010NUS Medical School Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6402-4288","authenticated-orcid":false,"given":"Choon Kiat","family":"Ong","sequence":"additional","affiliation":[{"name":"Lymphoma Genomic Translational Research Laboratory Division of Cellular &amp; Molecular Research National Cancer Centre Singapore Singapore City Singapore"},{"name":"Duke\u2010NUS Medical School Singapore City Singapore"},{"name":"Genome Institute of Singapore A*STAR"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404873"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02991"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13444"},{"key":"e_1_2_11_5_1","first-page":"9655","article-title":"PI3K\/AKT inhibition induces compensatory activation of the MET\/STAT3 pathway in non\u2010small cell lung cancer","volume":"15","author":"Bian C.","year":"2018","journal-title":"Oncology Letters"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13065"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2014.08.001"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx289"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2664"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-05-786566"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906461107"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29579"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314583"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-97"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110486108"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-872549"},{"key":"e_1_2_11_17_1","first-page":"2465","article-title":"The clinical significance of activated p\u2010AKT expression in peripheral T\u2010cell lymphoma","volume":"35","author":"Hong J.Y.","year":"2015","journal-title":"Anticancer Research"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-12-542142"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-08-802470"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-460832"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-537555"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-018-0138-7"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.068510"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-017-0004-x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073560"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw282"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-366203"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20864"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2036"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-01-829424"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.4558"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2014.01.007"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.16435","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.16435","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.16435","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.16435","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T05:38:47Z","timestamp":1693978727000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.16435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,31]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1111\/bjh.16435"],"URL":"https:\/\/doi.org\/10.1111\/bjh.16435","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,31]]},"assertion":[{"value":"2019-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}