{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T05:46:54Z","timestamp":1771912014104,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K15298"],"award-info":[{"award-number":["23K15298"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K19505"],"award-info":[{"award-number":["21K19505"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K24362"],"award-info":[{"award-number":["23K24362"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21ck0106607"],"award-info":[{"award-number":["JP21ck0106607"]}],"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":["JP24ck0106851"],"award-info":[{"award-number":["JP24ck0106851"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,5,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Kr\u00fcppel\u2010like factor 4 (KLF4) exhibits both oncogenic and tumor\u2010suppressive effects depending on the type of cancer and cellular context. In T\u2010cell acute lymphoblastic leukemia (T\u2010ALL),\n                    <jats:italic>KLF4<\/jats:italic>\n                    expression is silenced by promoter methylation, and the induction of KLF4 suppresses the proliferation of T\u2010ALL cells. Therefore, KLF4 is thought to function as a tumor suppressor in T\u2010ALL cells; however, its role in the differentiation of T\u2010ALL cells remains unclear. Here, we show that KLF4 induced T\u2010cell differentiation and apoptosis in TALL\u20101 cells harboring an activating mutation in NOTCH3. Mechanistically, KLF4 directly downregulated\n                    <jats:italic>NOTCH3<\/jats:italic>\n                    expression by binding to its promoter, thereby promoting the differentiation of CD4\/CD8 double\u2010positive cells into CD4 single\u2010positive cells, with the differentiated cells subsequently undergoing apoptosis. Furthermore, we found that APTO\u2010253, a small\u2010molecule inducer of KLF4, effectively suppressed cell growth in TALL\u20101 cells by promoting T\u2010cell differentiation followed by apoptotic cell death. These findings suggest a promising strategy for developing novel differentiation therapies for T\u2010ALL with NOTCH3 mutations.\n                  <\/jats:p>","DOI":"10.1096\/fj.202402997r","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T03:13:21Z","timestamp":1748056401000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Induction of T\u2010Cell Differentiation by\n                    <scp>KLF4<\/scp>\n                    in T\u2010Cell Acute Lymphoblastic Leukemia Cells Harboring Activating Mutation in\n                    <scp>NOTCH3<\/scp>"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1311-6908","authenticated-orcid":false,"given":"Mina","family":"Noura","sequence":"first","affiliation":[{"name":"Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiko","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Clinical Research Center National Hospital Organization Nagoya Medical Center  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Kiyoi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihiko","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30031-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10163556"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V72.2.567.567"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.10.3315.422k16_3315_3324"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.02.025"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01416-y"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.339"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-023-02913-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2017.1300896"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.133"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-5323(03)00007-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1076"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-1104"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-1209"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3909"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200012)16:6<518::AID-HUMU9>3.0.CO;2-Q"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.062050599"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2015.05.001"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abl5471"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2014.10.004"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922606117"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-020-00187-x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.7"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08878"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-015-0273-z"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-150049"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)08083-5"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202402997R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T22:48:13Z","timestamp":1761691693000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202402997R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,12]]},"references-count":28,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,5,31]]}},"alternative-id":["10.1096\/fj.202402997R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202402997r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,12]]},"assertion":[{"value":"2024-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70613"}}