{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T07:38:15Z","timestamp":1763105895219,"version":"3.40.5"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K16121","19K08868"],"award-info":[{"award-number":["18K16121","19K08868"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002369","name":"Chongqing University","doi-asserted-by":"publisher","award":["cquyjg21305","2022YJKYXM\u2010001","2022YJKYXM\u2010043"],"award-info":[{"award-number":["cquyjg21305","2022YJKYXM\u2010001","2022YJKYXM\u2010043"]}],"id":[{"id":"10.13039\/501100002369","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572634","82172682"],"award-info":[{"award-number":["81572634","82172682"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016834","name":"Chongqing Municipal Health Commission","doi-asserted-by":"publisher","award":["2020FYYX087"],"award-info":[{"award-number":["2020FYYX087"]}],"id":[{"id":"10.13039\/100016834","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002865","name":"Chongqing Science and Technology Commission","doi-asserted-by":"publisher","award":["cstc2019jcyj\u2010msxmX0358","cstc2020jcyj\u2010msxmX0951","cstc2021jcyj\u2010msxmX0909"],"award-info":[{"award-number":["cstc2019jcyj\u2010msxmX0358","cstc2020jcyj\u2010msxmX0951","cstc2021jcyj\u2010msxmX0909"]}],"id":[{"id":"10.13039\/501100002865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adult T\u2010cell leukemia\/lymphoma (ATL) is an intractable hematological malignancy with extremely poor prognosis. Recent studies have revealed that super\u2010enhancers (SE) play important roles in controlling tumor\u2010specific gene expression and are potential therapeutic targets for neoplastic diseases including ATL. Cyclin\u2010dependent protein kinase (CDK) 9 is a component of a complex comprising transcription factors (TFs) that bind the SE region. Alvocidib is a CDK9 inhibitor that exerts antitumor activity by inhibiting RNA polymerase (Pol) II phosphorylation and suppressing SE\u2010mediated, tumor\u2010specific gene expression. The present study demonstrated that alvocidib inhibited the proliferation of ATL cell lines and tumor cells from patients with ATL. RNA sequencing (RNA\u2010Seq) and chromatin immunoprecipitation sequencing (ChIP\u2010Seq) disclosed that SE regulated IRF4 in the ATL cell lines. Previous studies showed that IRF4 suppression inhibited ATL cell proliferation. Hence, IRF4 is a putative alvocidib target in ATL therapy. The present study revealed that SE\u2010mediated <jats:italic>IRF4<\/jats:italic> downregulation is a possible mechanism by which alvocidib inhibits ATL proliferation. Alvocidib also suppressed ATL in a mouse xenograft model. Hence, the present work demonstrated that alvocidib has therapeutic efficacy against ATL and partially elucidated its mode of action. It also showed that alvocidib is promising for the clinical treatment of ATL and perhaps other malignancies and neoplasms as well.<\/jats:p>","DOI":"10.1111\/cas.15550","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T13:53:46Z","timestamp":1662040426000},"page":"4092-4103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Alvocidib inhibits <scp>IRF4<\/scp> expression via super\u2010enhancer suppression and adult T\u2010cell leukemia\/lymphoma cell growth"],"prefix":"10.1111","volume":"113","author":[{"given":"Hikaru","family":"Sakamoto","sequence":"first","affiliation":[{"name":"Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"},{"name":"Department of Hematology Nagasaki University Hospital  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7607-4899","authenticated-orcid":false,"given":"Koji","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute Nagasaki University  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2954-5691","authenticated-orcid":false,"given":"Yoshitaka","family":"Imaizumi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute Nagasaki University  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Mishima","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Kitanosono","sequence":"additional","affiliation":[{"name":"Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeharu","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Hematology Nagasaki University Hospital  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Sawayama","sequence":"additional","affiliation":[{"name":"Department of Hematology Nagasaki University Hospital  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Hematology Nagasaki University Hospital  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Nagasaki Harbor Medical Center  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute Nagasaki University  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koh\u2010Ichiro","family":"Yoshiura","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"},{"name":"Division of Advanced Preventive Medical Sciences and Leading Medical Research Core Unit Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3683-7147","authenticated-orcid":false,"given":"Yasushi","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"},{"name":"Department of Hematology Nagasaki University Hospital  Nagasaki Japan"},{"name":"Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute Nagasaki University  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V50.3.481.481"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14658"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.9958"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.7732"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.3472"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-247510"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.93"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.036"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.053"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.03.054"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-792184"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.035"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-413021"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2538"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12408"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-741983"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2013.06.006"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2015.10.010"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428199609093442"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.7.1063"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1991.tb08051.x"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.f.353"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12921"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00300234"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.171"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-020735"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010722107"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3415"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.06.014"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019002639"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-020-00535-z"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006597"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-036368"},{"key":"e_1_2_12_36_1","first-page":"2482","article-title":"Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts","volume":"91","author":"Arguello F","year":"1998","journal-title":"Blood"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-01-761874"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000164"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.08.051"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.15550","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.15550","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.15550","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T21:19:43Z","timestamp":1692566383000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.15550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,3]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1111\/cas.15550"],"URL":"https:\/\/doi.org\/10.1111\/cas.15550","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"type":"print","value":"1347-9032"},{"type":"electronic","value":"1349-7006"}],"subject":[],"published":{"date-parts":[[2022,10,3]]},"assertion":[{"value":"2022-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}