{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:54:26Z","timestamp":1788965666634,"version":"build-2803163510"},"reference-count":57,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"42","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.science.org\/content\/page\/science-licenses-journal-article-reuse"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,10,17]]},"abstract":"<jats:p>\n                    Peripheral T cell lymphoma (PTCL) is a heterogeneous group of postthymic T cell neoplasms, with ~40% classified as PTCL\u2013not otherwise specified (PTCL-NOS). PTCL-GATA3, a molecularly defined subtype, associated with T helper 2 (T\n                    <jats:sub>H<\/jats:sub>\n                    2)\u2013like differentiation and poor prognosis, has frequent co-occurrence of\n                    <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                    loss\/mutation and heterozygous\n                    <jats:italic toggle=\"yes\">PTEN<\/jats:italic>\n                    loss. CD4+ T cell conditional mouse models with\n                    <jats:italic toggle=\"yes\">Trp53<\/jats:italic>\n                    mutation\/deletion and\n                    <jats:italic toggle=\"yes\">Pten<\/jats:italic>\n                    loss demonstrated mature T cell lymphomas (mTCLs) with T\n                    <jats:sub>H<\/jats:sub>\n                    2-like transcriptomic and immunophenotypic profiles. Molecular studies revealed that codeletion of\n                    <jats:italic toggle=\"yes\">Trp53\/Pten<\/jats:italic>\n                    induced T cell receptor and Janus kinase\u2013signal transducer and activator of transcription signaling, promoting T\n                    <jats:sub>H<\/jats:sub>\n                    2 differentiation while inhibiting T\n                    <jats:sub>H<\/jats:sub>\n                    1 differentiation. These findings were validated by CRISPR editing of\n                    <jats:italic toggle=\"yes\">TP53\/PTEN<\/jats:italic>\n                    loss in human CD4+ T cells and mechanistically evaluated the p53 binding region in intron-3 of GATA3, resulting in transcriptional repression. Transcriptomic profiles of m-TCLs recapitulated human-PTCL-GATA3 transcriptome and distinguished PTCL-NOS subtypes. Preclinical assessment of m-TCLs with PI3K\u03b3\/\u03b4 inhibitors significantly improved survival, supporting a therapeutic approach for the p53-aberrant PTCL-GATA3.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adx6877","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T17:58:56Z","timestamp":1760723936000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Cooperative role of distinctive TP53 and PTEN combined loss in the peripheral T cell lymphoma\u2013GATA3 molecular subgroup"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3078-614X","authenticated-orcid":true,"given":"Waseem G.","family":"Lone","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1677-0814","authenticated-orcid":true,"given":"Xuxiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."},{"name":"Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2750-6741","authenticated-orcid":true,"family":"Dylan T. Jochum","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1324-6678","authenticated-orcid":true,"given":"Alyssa","family":"Bouska","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-2734","authenticated-orcid":true,"given":"Kunal","family":"Shetty","sequence":"additional","affiliation":[{"name":"Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Herek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunandini","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5375-7515","authenticated-orcid":true,"given":"Chengfeng","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5779-154X","authenticated-orcid":true,"given":"Rauf","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."},{"name":"Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaina W.","family":"Nasser","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0352-5526","authenticated-orcid":true,"given":"Catalina","family":"Amador","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."},{"name":"Department of Pathology, University of Miami, Miami, FL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiza","family":"Arif","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2897-4419","authenticated-orcid":true,"given":"Abdul Rouf","family":"Mir","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayla B.","family":"Heavican-Foral","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2808-1749","authenticated-orcid":true,"given":"R. Katherine","family":"Hyde","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-8045","authenticated-orcid":true,"given":"Mamiko","family":"Sakata-Yanagimoto","sequence":"additional","affiliation":[{"name":"Division of Advanced Hemato-Oncology, Transborder Medical Research Center, University of Tsukuba, Tsukuba, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3949-8566","authenticated-orcid":true,"given":"Satyanarayana","family":"Rachagani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-3074","authenticated-orcid":true,"given":"Timothy W.","family":"McKeithan","sequence":"additional","affiliation":[{"name":"Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0435-5947","authenticated-orcid":true,"given":"David W.","family":"Scott","sequence":"additional","affiliation":[{"name":"British Columbia Cancer, Vancouver, BC V5Z 4E6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1735-2892","authenticated-orcid":true,"given":"Louis M.","family":"Staudt","sequence":"additional","affiliation":[{"name":"Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Inghirami","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Weil Cornell Medical College, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5009-4808","authenticated-orcid":true,"given":"Andrew","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-8328","authenticated-orcid":true,"given":"Timothy","family":"Greiner","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-7434","authenticated-orcid":true,"given":"Julie M.","family":"Vose","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Rimsza","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Scottsdale, AZ, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2621-3584","authenticated-orcid":true,"given":"Joesph","family":"Khoury","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6243-6008","authenticated-orcid":true,"given":"Wing C.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3668-0629","authenticated-orcid":true,"given":"Javeed","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.4558"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023021787"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-12-516245"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023021786"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-536359"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-227579"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-643569"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.06.006"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80702-3"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-12-544809"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000779"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-872549"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.262659"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.01.030"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-206722"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00021-7"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00323-9"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.4.1563"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.252148.114"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1282"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20150794"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11412"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.01.039"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11125"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-1113"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00650.x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102116"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3076"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.04.006"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.22810"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1798"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-1808"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.12.013"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.03.022"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1349-1"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.07.013"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42382"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.8.2610"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.07.053"},{"key":"e_1_3_2_41_2","first-page":"52739","article-title":"Mouse naive CD4+ T cell isolation and in vitro differentiation into T cell subsets","volume":"98","author":"Flaherty S.","year":"2015","unstructured":"S. Flaherty, J. M. Reynolds, Mouse naive CD4+ T cell isolation and in vitro differentiation into T cell subsets. J. Vis. Exp. 98, 52739 (2015).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000142249.08135.e9"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.143"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.220533.117"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.255"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-022-00745-y"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00134-0"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2405056"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80084-9"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adh1436"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.07.028"},{"key":"e_1_3_2_52_2","first-page":"637","article-title":"STAT3 and p53: Dual target for cancer therapy","volume":"8","author":"Pham T. H.","year":"2020","unstructured":"T. H. Pham, H. M. Park, J. Kim, J. T. Hong, D. Y. Yoon, STAT3 and p53: Dual target for cancer therapy. Biomedicine 8, 637 (2020).","journal-title":"Biomedicine"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-11-742577"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.2.684"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.13.6065"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03076-6"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.12.009"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"}],"updated-by":[{"DOI":"10.1126\/sciadv.aeg5995","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000}}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adx6877","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adx6877","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:58:08Z","timestamp":1774029488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adx6877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":57,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2025,10,17]]}},"alternative-id":["10.1126\/sciadv.adx6877"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adx6877","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]},"assertion":[{"value":"2025-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadx6877"}}