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In addition, we included one case with a good initial treatment response and on\u2010treatment relapse at the end of upfront therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed a dynamic clonal evolution in all cases, with relapse almost exclusively originating from a subclone at diagnosis. We identified several driver mutations that may have influenced the outgrowth of a minor clone at diagnosis to become the major clone at relapse. For example, a minimal residual disease (MRD)\u2010based standard\u2010risk patient with <jats:italic>ETV6\u2010RUNX1<\/jats:italic>\u2010positive leukemia developed a relapse from a <jats:italic>TP53<\/jats:italic>\u2010mutated subclone after loss of the wildtype allele. Furthermore, two patients with <jats:italic>TCF3\u2010PBX1\u2010<\/jats:italic>positive leukemia that developed a very early relapse carried E1099K <jats:italic>WHSC1<\/jats:italic> mutations at diagnosis, a hotspot mutation that was recurrently encountered in other very early <jats:italic>TCF3\u2010PBX1<\/jats:italic>\u2010positive leukemia relapses as well. In addition to alterations in known relapse drivers, we found two cases with truncating mutations in the cohesin gene <jats:italic>RAD21<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Comprehensive genomic characterization of diagnosis\u2013relapse pairs shows that very early relapses in BCP\u2010ALL frequently arise from minor subclones at diagnosis. A detailed understanding of the therapeutic pressure driving these events may aid the development of improved therapies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29361","type":"journal-article","created":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T01:24:21Z","timestamp":1633137861000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clonal dynamics in pediatric B\u2010cell precursor acute lymphoblastic leukemia with very early relapse"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9398-2637","authenticated-orcid":false,"given":"\u017deljko","family":"Anti\u0107","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"},{"name":"Department of Human Genetics Hannover Medical School  Hannover 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