{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T16:59:20Z","timestamp":1776272360071,"version":"3.50.1"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370212"],"award-info":[{"award-number":["82370212"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>ETV6<\/jats:italic>::<jats:italic>RUNX1<\/jats:italic> is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low\u2010risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low\u2010risk <jats:italic>ETV6<\/jats:italic>::<jats:italic>RUNX1<\/jats:italic>\u2010positive B\u2010cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome\u2010wide transcriptome and single\u2010nucleotide variants. We found high <jats:italic>TIMD4<\/jats:italic> expression\u00a0(&gt;\u00a085th\u2010percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR]\u00a0=\u00a05.07 [1.76, 14.62]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.03). In an independent validation cohort of low\u2010risk <jats:italic>ETV6<\/jats:italic>::<jats:italic>RUNX1<\/jats:italic>\u2010positive B\u2010cell ALL (<jats:italic>N<\/jats:italic>\u00a0=\u00a068) high <jats:italic>TIMD4<\/jats:italic> expression at diagnosis had an HR\u00a0=\u00a04.78 [1.07, 21.36] (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.04) for early relapse. In another validation cohort including 78 children with low\u2010risk <jats:italic>ETV6<\/jats:italic>::<jats:italic>RUNX1<\/jats:italic>\u2010negative B\u2010cell ALL, high <jats:italic>TIMD4<\/jats:italic> expression at diagnosis had an HR\u00a0=\u00a03.93 [1.31, 11.79] (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.01). Our results suggest high <jats:italic>TIMD4<\/jats:italic> expression at diagnosis in low\u2010risk B\u2010cell ALL in children might be associated with high risk for early relapse.<\/jats:p>","DOI":"10.1002\/jha2.872","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T02:22:43Z","timestamp":1710555763000},"page":"333-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gene expression prognostic of early relapse risk in low\u2010risk B\u2010cell acute lymphoblastic leukaemia in children"],"prefix":"10.1002","volume":"5","author":[{"given":"Xiaowen","family":"Gong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Tianjin 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