{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:46:43Z","timestamp":1774928803337,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The role of glycogen synthase kinase (GSK)\u20103\u03b2 in adult T\u2010cell leukemia (ATL) caused by human T\u2010cell leukemia virus type 1 (HTLV\u20101) is paradoxical and enigmatic. Here, we investigated the role of GSK\u20103\u03b2 and its potential as a therapeutic target for ATL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cell proliferation\/survival, cell cycle, apoptosis, and reactive oxygen species (ROS) generation were examined using the WST\u20108 assay, flow cytometry, and Hoechst 33342 staining, respectively. Expression of GSK\u20103\u03b2 and cell cycle\/death\u2010related proteins, and survival signals was analyzed using RT\u2010PCR, immunofluorescence staining, and immunoblotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HTLV\u20101\u2010infected T\u2010cell lines showed nuclear accumulation of GSK\u20103\u03b2. GSK\u20103\u03b2 knockdown and its inhibition with 9\u2010ING\u201041 and LY2090314 suppressed cell proliferation\/survival. 9\u2010ING\u201041 induced G2\/M arrest by enhancing the expression of \u03b3H2AX, p53, p21, and p27, and suppressing the expression of CDK1, cyclin A\/B, and c\u2010Myc. It induced caspase\u2010mediated apoptosis by decreasing the expression of Bcl\u2010xL, Mcl\u20101, XIAP, c\u2010IAP1\/2, and survivin, and increasing the expression of Bak and Bax. 9\u2010ING\u201041 also induced ferroptosis and necroptosis, promoted JNK phosphorylation, and suppressed IKK\u03b3 and JunB expression. It inhibited the phosphorylation of I\u03baB\u03b1, Akt, and STAT3\/5, induced ROS production, and reduced glycolysis\u2010derived lactate levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>GSK\u20103\u03b2 functions as an oncogene in ATL and could be a potential therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.14300","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T11:09:28Z","timestamp":1725620968000},"page":"852-862","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A New Strategy for Adult T\u2010Cell Leukemia Treatment Targeting Glycogen Synthase Kinase\u20103\u03b2"],"prefix":"10.1111","volume":"113","author":[{"given":"Chie","family":"Ishikawa","sequence":"first","affiliation":[{"name":"Department of Microbiology and Oncology Graduate School of Medicine, University of the Ryukyus  Nishihara Japan"},{"name":"Division of Health Sciences, Transdisciplinary Research Organization for Subtropics and Island Studies University of the Ryukyus  Nishihara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3998-6711","authenticated-orcid":false,"given":"Naoki","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Oncology Graduate School of Medicine, University of the Ryukyus  Nishihara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-023-03547-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01207"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-021-01138-3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-023-03572-4"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2240"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9061388"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2021.100779"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/505607"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.04.012"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12540"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4624"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2022.2088984"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.9.3980"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-020-01007-z"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1990.tb02554.x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910480423"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2015.2848"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0125028"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16061220"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.01.004"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.08.003"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2015.10.012"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11111812"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114301"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232214133"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.21185.1"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v12.i6.481"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2014.03.013"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.03.015"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22414"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2015.16.6.2129"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-008-0208-7"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02686"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.02.019"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2399-y"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0752-3"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01433-5"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep38553"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-019-05239-3"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802481200"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22685"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201701314R"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009585"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2020.102243"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3289"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12519"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-1916"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01352-x"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11154"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.14300","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T02:31:33Z","timestamp":1730860293000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.14300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":49,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/ejh.14300"],"URL":"https:\/\/doi.org\/10.1111\/ejh.14300","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,6]]},"assertion":[{"value":"2024-04-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}