{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:39:15Z","timestamp":1792931955126,"version":"4.5.0"},"reference-count":77,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP17 cm0106407h0002"],"award-info":[{"award-number":["JP17 cm0106407h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatrics International"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neonates with Down syndrome (<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>) have a propensity to develop the unique myeloproliferative disorder, transient abnormal myelopoiesis (<jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> usually resolves spontaneously in \u22643 months, but approximately 10% of patients with <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> die from hepatic or multi\u2010organ failure. After remission, 20% of patients with <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> develop acute myeloid leukemia associated with Down syndrome (<jats:styled-content style=\"fixed-case\">ML<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>). Blasts in both <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ML<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> have trisomy 21 and <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content> binding protein 1<\/jats:italic> (<jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>1<\/jats:italic>) mutations. Recent studies have shown that infants with <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> and no clinical signs of <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> or increases in peripheral blood blasts can have minor clones carrying <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>1<\/jats:italic> mutations, referred to as silent <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content>. Low\u2010dose cytarabine can improve the outcomes of patients with <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> and high white blood cell count. A number of studies using fetal liver cells, mouse models, or induced pluripotent stem cells have elucidated the roles of trisomy 21 and <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>1<\/jats:italic> mutations in the development of <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content>. Next\u2010generation sequencing of <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ML<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> patient samples identified additional mutations in genes involved in epigenetic regulation. Xenograft models of <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> demonstrate the genetic heterogeneity of <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> blasts and mimic the process of clonal selection and expansion of <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> clones that leads to <jats:styled-content style=\"fixed-case\">ML<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation analysis suggests that epigenetic dysregulation may be involved in the progression from <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">ML<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>. Unraveling the mechanisms underlying leukemogenesis and identification of factors that predict progression to leukemia could assist in development of strategies to prevent progression to <jats:styled-content style=\"fixed-case\">ML<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>. Investigation of <jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content>, a unique pre\u2010leukemic condition, will continue to strongly influence basic and clinical research into the development of hematological malignancies.<\/jats:p>","DOI":"10.1111\/ped.13776","type":"journal-article","created":{"date-parts":[[2018,12,29]],"date-time":"2018-12-29T07:40:40Z","timestamp":1546069240000},"page":"222-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Recent advances in the understanding of transient abnormal myelopoiesis in Down syndrome"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8892-3082","authenticated-orcid":false,"given":"Kenichiro","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology Shizuoka Children's Hospital Aoi-ku Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/08880019209018329"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2448"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-118810"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07231.x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-350017"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0146-0005(97)80025-0"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng955"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2003.08.001"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13266-7"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0013"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3599"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-02-0390"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3383"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12041"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2012.02.010"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-016-0338-x"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-016-1959-5"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-12-474387"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2759"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(20000415)42:2<118::AID-CYTO6>3.0.CO;2-E"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1309\/XREF-C9T2-6U0A-4EDT"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-836510"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-515148"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990604)84:4<340::AID-AJMG6>3.0.CO;2-N"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-069542"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-994424"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3109\/08880019609033374"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1718"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2014-308004"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncponc0876"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2010.06.012"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.258"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.48.10.973"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-911X(199809)31:3<159::AID-MPO6>3.0.CO;2-A"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-013-1487-5"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2008.01061.x"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.03093.x"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.373"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.13093"},{"key":"e_1_2_12_41_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1182\/blood.V72.1.15.15","article-title":"Cytogenetic findings and clinical features in acute leukemia and transient myeloproliferative disorder in Down's syndrome","volume":"72","author":"Hayashi Y","year":"1988","journal-title":"Blood"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2456"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.1311.1311"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018018945"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003586107"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-157859"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-152967"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211405109"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201439583"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211175109"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1215468109"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.04.031"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1159\/000472398"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.047373"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511150103"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-174813"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60455"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-013-1347-3"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-085670"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-161422"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-227629"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.21.9623"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.4.1215-1227.2005"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-687889"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2017.1361525"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0075"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-405746"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1566"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2009.01338.x"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2740"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-282426"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-114231"},{"key":"e_1_2_12_73_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1182\/blood.V126.23.89.89","article-title":"Dysregulation of DNA methylation involves in progression of myeloid leukemia in Down syndrome","volume":"126","author":"Saida S","year":"2015","journal-title":"Blood"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevOncog.v16.i1-2.40"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.959840"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.06.023"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mph.0000212997.02554.f6"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10762"}],"container-title":["Pediatrics International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fped.13776","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ped.13776","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ped.13776","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ped.13776","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T05:16:27Z","timestamp":1694409387000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ped.13776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":77,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1111\/ped.13776"],"URL":"https:\/\/doi.org\/10.1111\/ped.13776","archive":["Portico"],"relation":{},"ISSN":["1328-8067","1442-200X"],"issn-type":[{"value":"1328-8067","type":"print"},{"value":"1442-200X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"2018-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}