{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:29:06Z","timestamp":1791822546130,"version":"4.3.4"},"reference-count":32,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"29","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2024,10,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Although cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 90%, ALL remains a leading cause of cancer death in children. Half of relapses arise in children initially classified with standard-risk (SR) disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>To identify genomic determinants of relapse in children with SR ALL, we performed genome and transcriptome sequencing of diagnostic and remission samples of children with SR (n = 1,381) or high-risk B-ALL with favorable cytogenetic features (n = 115) enrolled on Children's Oncology Group trials. We used a case-control study design analyzing 439 patients who relapsed and 1,057 who remained in complete remission for at least 5 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Genomic subtype was associated with relapse, which occurred in approximately 50% of cases of\n                      <jats:italic>PAX5<\/jats:italic>\n                      -altered ALL (odds ratio [OR], 3.31 [95% CI, 2.17 to 5.03];\n                      <jats:italic>P =<\/jats:italic>\n                      3.18 \u00d7 10\n                      <jats:sup>\u20138<\/jats:sup>\n                      ). Within high-hyperdiploid ALL, gain of chromosome 10 with disomy of chromosome 7 was associated with favorable outcome (OR, 0.27 [95% CI, 0.17 to 0.42];\n                      <jats:italic>P<\/jats:italic>\n                      = 8.02 \u00d7 10\n                      <jats:sup>\u201310<\/jats:sup>\n                      ; St Jude Children's Research Hospital validation cohort: OR, 0.22 [95% CI, 0.05 to 0.80];\n                      <jats:italic>P<\/jats:italic>\n                      = .009), and disomy of chromosomes 10 and 17 with gain of chromosome 6 was associated with relapse (OR, 7.16 [95% CI, 2.63 to 21.51];\n                      <jats:italic>P<\/jats:italic>\n                      = 2.19 \u00d7 10\n                      <jats:sup>\u20135<\/jats:sup>\n                      ; validation cohort: OR, 21.32 [95% CI, 3.62 to 119.30];\n                      <jats:italic>P<\/jats:italic>\n                      = .0004). Genomic alterations were associated with relapse in a subtype-dependent manner, including alterations of\n                      <jats:italic>INO80<\/jats:italic>\n                      in\n                      <jats:italic>ETV6::RUNX1<\/jats:italic>\n                      ALL,\n                      <jats:italic>IKZF1<\/jats:italic>\n                      , and\n                      <jats:italic>CREBBP<\/jats:italic>\n                      in high-hyperdiploid ALL and\n                      <jats:italic>FHIT<\/jats:italic>\n                      in\n                      <jats:italic>BCR::ABL1<\/jats:italic>\n                      -like ALL. Genomic alterations were also associated with the presence of minimal residual disease, including\n                      <jats:italic>NRAS<\/jats:italic>\n                      and\n                      <jats:italic>CREBBP<\/jats:italic>\n                      in high-hyperdiploid ALL.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Genetic subtype, patterns of aneuploidy, and secondary genomic alterations determine risk of relapse in childhood ALL. Comprehensive genomic analysis is required for optimal risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.23.02238","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T16:03:40Z","timestamp":1723219420000},"page":"3491-3503","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":76,"title":["Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia"],"prefix":"10.1200","volume":"42","clinical-trial-number":[{"clinical-trial-number":"nct00103285","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01190930","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00075725","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00549848","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02883049","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00137111","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5302-9147","authenticated-orcid":false,"given":"Ti-Cheng","family":"Chang","sequence":"first","affiliation":[{"name":"Center for Applied Bioinformatics, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-2368","authenticated-orcid":false,"given":"Wenan","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Applied Bioinformatics, St Jude Children's Research Hospital, Memphis, TN"},{"name":"Division of Computational Biology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxu","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Pathology, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongshan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Center for Applied Bioinformatics, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Hedges","sequence":"additional","affiliation":[{"name":"Center for Applied Bioinformatics, St Jude 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of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8547-1658","authenticated-orcid":false,"given":"Elizabeth A.","family":"Raetz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Perlmutter Cancer Center, NYU Langone Hospital, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1099-3478","authenticated-orcid":false,"given":"Meenakshi","family":"Devidas","sequence":"additional","affiliation":[{"name":"Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, St Jude Children's Research Hospital, Memphis, 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