{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:16:34Z","timestamp":1747185394998,"version":"3.40.5"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970135","81870114"],"award-info":[{"award-number":["81970135","81870114"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Relapse remained the major obstacle to improving the prognosis of children with acute lymphoblastic leukemia (ALL). This study aimed to investigate the changing patterns of <jats:italic>Ig<\/jats:italic>\/<jats:italic>TCR<\/jats:italic> gene rearrangements between diagnosis and relapse and the clinical relevance and to explore the mechanism of leukemic relapse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clonal <jats:italic>Ig<\/jats:italic>\/<jats:italic>TCR<\/jats:italic> gene rearrangements were screened by multiplex PCR amplification in 85 paired diagnostic and relapse bone marrow (BM) samples from children with ALL. The new rearrangements presented at relapse were quantitatively assessed by the RQ\u2010PCR approach targeting the patient\u2010specific junctional region sequence in 19 diagnostic samples. The relapse clones were further back\u2010traced to diagnostic and follow\u2010up BM samples from 12 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Comparison of <jats:italic>Ig<\/jats:italic>\/<jats:italic>TCR<\/jats:italic> gene rearrangements between diagnosis and relapse showed that 40 (57.1%) B\u2010ALL and 5 (33.3%) T\u2010ALL patients exhibited a change from diagnosis to relapse, and 25 (35.7%) B\u2010ALL patients acquired new rearrangements at relapse. The new relapse rearrangements were present in 15 of the 19 (78.9%) diagnostic samples as shown by RQ\u2010PCR, with a median level of 5.26\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup>. The levels of minor rearrangements correlated with B immunophenotype, WBC counts, age at diagnosis, and recurrence time. Furthermore, back\u2010tracing rearrangements in 12 patients identified three patterns of relapse clone dynamics, which suggested the recurrence mechanisms not only through clonal selection of pre\u2010existing subclones but also through an ongoing clonal evolution during remission and relapse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Backtracking <jats:italic>Ig<\/jats:italic>\/<jats:italic>TCR<\/jats:italic> gene rearrangements in relapse clones of pediatric ALL revealed complex patterns of clonal selection and evolution for leukemic relapse.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.14100","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T08:45:56Z","timestamp":1684313156000},"page":"717-725","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tracing back of relapse clones by <i>Ig<\/i>\/<i>TCR<\/i> gene rearrangements reveals complex patterns 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