{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:50:58Z","timestamp":1792158658019,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K17414"],"award-info":[{"award-number":["20K17414"]}],"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":["24K19214"],"award-info":[{"award-number":["24K19214"]}],"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":["19K08350"],"award-info":[{"award-number":["19K08350"]}],"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":["25K10516"],"award-info":[{"award-number":["25K10516"]}],"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":["23K07847"],"award-info":[{"award-number":["23K07847"]}],"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":["JP19ck0106253"],"award-info":[{"award-number":["JP19ck0106253"]}],"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":["JP22ck0106634"],"award-info":[{"award-number":["JP22ck0106634"]}],"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":["JP24ck0106853"],"award-info":[{"award-number":["JP24ck0106853"]}],"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":["15ck0106066h0002"],"award-info":[{"award-number":["15ck0106066h0002"]}],"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":["JP16ck0106064"],"award-info":[{"award-number":["JP16ck0106064"]}],"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":["JP19ck0106329"],"award-info":[{"award-number":["JP19ck0106329"]}],"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":["19ek0109348s0102"],"award-info":[{"award-number":["19ek0109348s0102"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012045","name":"Kawano Masanori Memorial Public Interest Incorporated Foundation","doi-asserted-by":"publisher","award":["2024\u201035"],"award-info":[{"award-number":["2024\u201035"]}],"id":[{"id":"10.13039\/100012045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017682","name":"Japanese Society of Hematology","doi-asserted-by":"publisher","award":["2023\u201023058"],"award-info":[{"award-number":["2023\u201023058"]}],"id":[{"id":"10.13039\/100017682","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017682","name":"Japanese Society of Hematology","doi-asserted-by":"publisher","award":["2024\u201024066"],"award-info":[{"award-number":["2024\u201024066"]}],"id":[{"id":"10.13039\/100017682","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020237","name":"Japan Health Research Promotion Bureau","doi-asserted-by":"publisher","award":["2024\u2010B\u201008"],"award-info":[{"award-number":["2024\u2010B\u201008"]}],"id":[{"id":"10.13039\/100020237","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","award":["30\u201014B"],"award-info":[{"award-number":["30\u201014B"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","award":["2021B\u201015"],"award-info":[{"award-number":["2021B\u201015"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    We conducted a multiomics analysis of paediatric acute promyelocytic leukaemia (APL) in 36 patients enrolled in the Japanese AML\u2010P05 study. Targeted deep sequencing identified\n                    <jats:italic>EP300<\/jats:italic>\n                    mutations (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092) and\n                    <jats:italic>MYC<\/jats:italic>\n                    \u2010internal tandem duplication (ITD) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091), which have not been previously reported in APLs. DNA methylation analysis classified 34 paediatric APLs into two groups: hypermethylation and hypomethylation. Patients in the hypermethylation group had significantly worse outcomes compared to those in the hypomethylation group (3\u2010year overall survival: 80% vs. 100%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.043; 3\u2010year event\u2010free survival: 73% vs. 95%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.049). Remarkably, the EBF1\u2010binding motif was enriched in 82.3% of the CpG sites that were differentially methylated between the hyper\u2010 and hypomethylation groups, and these sites were predominantly located in enhancer regions. Among the 1427 genes that were significantly differentially expressed between the two groups,\n                    <jats:italic>EP300<\/jats:italic>\n                    was significantly downregulated in the hypermethylation group. Pathway analyses revealed global transcriptional downregulation in the hypermethylation group; however,\n                    <jats:italic>MYC<\/jats:italic>\n                    , a known\n                    <jats:italic>EP300<\/jats:italic>\n                    \u2010repressed gene, was upregulated within the G2M checkpoint. Our findings suggest a potential link among enhancer\u2010based epigenetic dysregulation involving DNA methylation at EBF1\u2010binding sites,\n                    <jats:italic>EP300<\/jats:italic>\n                    dysfunction and\n                    <jats:italic>MYC<\/jats:italic>\n                    activation. These alterations may contribute to disease heterogeneity and prognosis in paediatric APL.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70733","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:59:15Z","timestamp":1786409955000},"page":"1586-1597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiomics analysis focusing on genome\u2010wide\n                    <scp>DNA<\/scp>\n                    methylation in paediatric acute promyelocytic leukaemia"],"prefix":"10.1111","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6089-5522","authenticated-orcid":false,"given":"Etsuko","family":"Murayama","sequence":"first","affiliation":[{"name":"Department of Pediatrics Gunma University Graduate School of Medicine  Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8137-0334","authenticated-orcid":false,"given":"Tomoko","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Maternal\u2010Fetal Biology National Research Institute for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-0753","authenticated-orcid":false,"given":"Genki","family":"Yamato","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gunma University Graduate School of Medicine  Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0392-9221","authenticated-orcid":false,"given":"Norio","family":"Shiba","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yokohama City University  Yokohama Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2838-4555","authenticated-orcid":false,"given":"Kentaro","family":"Ohki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Research National Research Institute for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7271-3454","authenticated-orcid":false,"given":"Yusuke","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gunma University Graduate School of Medicine  Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeko","family":"Kaburagi","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Gunma Children's Medical Center  Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2169-0787","authenticated-orcid":false,"given":"Takumi","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gunma University Graduate School of Medicine  Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohide","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Gunma Children's Medical Center  Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Division of Cancer Evolution National Cancer Center Research Institute  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-0992","authenticated-orcid":false,"given":"Yasuhito","family":"Nannya","sequence":"additional","affiliation":[{"name":"Division of Hematopoietic Disease Control, Institute of Medical Science The University of Tokyo  Tokyo Japan"},{"name":"Department of Pathology and Tumor Biology Kyoto University Graduate School of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1520-7007","authenticated-orcid":false,"given":"Daisuke","family":"Tomizawa","sequence":"additional","affiliation":[{"name":"Division of Leukemia and Lymphoma, Children's Cancer Center National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Taga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shiga University of Medical Science  Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souichi","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences Kyoto University Graduate School of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Yuza","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Tokyo Metropolitan Children's Medical Center  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Toho University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seishi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Tumor Biology Kyoto University Graduate School of Medicine  Kyoto Japan"},{"name":"Institute for the Advanced Study of Human Biology (WPI\u2010ASHBi) Kyoto University  Kyoto Japan"},{"name":"Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhide","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Gunma Children's Medical Center  Gunma Japan"},{"name":"Institute of Physiology and Medicine Jobu University  Isesaki Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90113-D"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-03-836528"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08332.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.6183"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18618"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.5206"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25573"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-021-02625-6"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2014.19"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.69"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0338-z"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02478-2"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024015275"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-08-448860"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301689"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30626"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005381"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14068"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-021-01207-1"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.107"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1180"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty902"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab996"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.013243"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36262-0"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008280"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2493-4"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14489"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112422"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20212437"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.008"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.12.4699"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00504-5"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.147942.112"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.07.041"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2021.106733"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4439"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1464158"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009564"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.081141998"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.70733","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.70733","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.70733","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:09:14Z","timestamp":1792156154000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.70733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/bjh.70733"],"URL":"https:\/\/doi.org\/10.1111\/bjh.70733","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"assertion":[{"value":"2026-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}