{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:04:39Z","timestamp":1793361879193,"version":"4.5.0"},"posted":{"date-parts":[[2025,11,6]]},"group-title":"Genetic and Genomic Medicine","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["P30 CA021765"],"award-info":[{"award-number":["P30 CA021765"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 CA276079"],"award-info":[{"award-number":["R01 CA276079"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018154","name":"Fund for Innovation in Cancer Informatics","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018154","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Relapse remains the leading cause of mortality in pediatric acute myeloid leukemia (pAML), yet the genetic changes contributing to relapse remain incompletely defined. We performed whole-genome and targeted-capture sequencing of 41 pediatric AML cases with paired relapse samples. Mutational burden increased at relapse, whereas therapy-related mutational signatures were rarely observed and only occasionally associated with pathogenic mutations. Although recurrently enriched mutations at relapse included those in\n                  <jats:italic>FLT3<\/jats:italic>\n                  ,\n                  <jats:italic>WT1<\/jats:italic>\n                  , and\n                  <jats:italic>TP53<\/jats:italic>\n                  , relapse-fated subclones were frequently marked only by non-pathogenic or non-coding variants. Longitudinal deep sequencing (\u223c5000X) coupled with paired serial monitoring by WGS (\u223c100X) in eight patients showed rapid depletion of major clones after induction therapy, whereas subclones often displayed variable chemosensitivity. Relapse-specific mutations emerged only late, suggesting that selection of pre-existing clones is the predominant mechanism of relapse. Together, our data indicate that pAML relapse arises through the selection of pre-existing clones with diverse trajectories.\n                <\/jats:p>","DOI":"10.1101\/2025.11.04.25339472","type":"posted-content","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T20:20:19Z","timestamp":1762460419000},"source":"Crossref","is-referenced-by-count":2,"title":["Genetic Evolution of Pediatric Acute Myeloid Leukemia and Its Contribution to Disease Relapse"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5636-6602","authenticated-orcid":false,"given":"Masayuki","family":"Umeda","sequence":"first","affiliation":[{"name":"Department of Pathology, St. Jude Children\u2019s Research Hospital, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-0076","authenticated-orcid":false,"given":"Pandurang","family":"Kolekar","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, St. Jude 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