{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:50:00Z","timestamp":1787503800999,"version":"build-2736575974"},"reference-count":25,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>We comprehensively profiled the landscape of immunoglobulin (IG) and T-cell receptor (TR) rearrangements at diagnosis in 1212 patients with acute lymphoblastic leukemia (ALL; 573 children and 639 adults) diagnosed in Germany between 2017 and 2022. Our study revealed a significant age-related decrease in immunogenetic maturation, where IG \u03ba rearrangements in B-ALL and complete TR \u03b2\/\u03b4 rearrangements in T-ALL, hallmarks of maturity, were more frequent in pediatric patients compared to adults (B-ALL: 68.7% vs 39.0%, P &amp;lt; 2.2e-16; T-ALL: 85.7% vs 67.3%, P = 6.7e-03). Compared to adults, children had a higher average number of IG\/TR markers per patient (6 vs 4; P = 2.5e-38) and markedly fewer lacked these markers (0.5% compared to 6.7%). IG heavy chain clonal evolution was most pronounced among pro-B-ALL cases (60.9%), with the V-to-DJ mechanism driving pro-B evolution (78.6%), whereas V-replacement dominated other immunophenotypes. Furthermore, expanded accompanying T-cell clones of unknown significance in B-ALL increased with age. This next-generation sequencing-based study offers an unprecedented characterization of IG\/TR rearrangement patterns across ALL subtypes and age groups. It highlights the higher immunogenetic maturity in children, which may be explained by the infection-driven abnormal activity of the IG\/TR recombination machinery in pediatric ALL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024027175","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T22:24:21Z","timestamp":1742941461000},"page":"585-589","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":6,"title":["NGS-based IG\/TR gene rearrangement profiling in acute lymphoblastic leukemia: age dependence of immunogenetic maturation"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5394-1072","authenticated-orcid":false,"given":"Michaela","family":"Kotrov\u00e1","sequence":"first","affiliation":[{"name":"1Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Kiel, Germany"},{"name":"2University Cancer Center Schleswig-Holstein, Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Proske","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Kiel, Germany"},{"name":"2University Cancer Center Schleswig-Holstein, Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikos","family":"Darzentas","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Kiel, Germany"},{"name":"2University Cancer Center Schleswig-Holstein, Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Laqua","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Kiel, Germany"},{"name":"2University Cancer Center Schleswig-Holstein, Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Kehden","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Kiel, Germany"},{"name":"2University Cancer Center Schleswig-Holstein, Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-1160","authenticated-orcid":false,"given":"Jan","family":"K\u00e4ssens","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Kiel, Germany"},{"name":"2University Cancer Center Schleswig-Holstein, Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Bendig","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Kiel, Germany"},{"name":"2University Cancer 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Wessels","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Kiel, Germany"},{"name":"2University Cancer Center Schleswig-Holstein, Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljko","family":"Antic","sequence":"additional","affiliation":[{"name":"4Institute of Human Genetics, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Pott","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Kiel, Germany"},{"name":"2University Cancer Center Schleswig-Holstein, Campus Kiel, Kiel, 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M.","family":"van Dongen","sequence":"additional","affiliation":[{"name":"5European Scientific Foundation for Laboratory Hemato-Oncology, Zutphen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2291-8245","authenticated-orcid":false,"given":"Nicola","family":"G\u00f6kbuget","sequence":"additional","affiliation":[{"name":"6Department of Hematology and Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9609-4643","authenticated-orcid":false,"given":"Guranda","family":"Chitadze","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Kiel, Germany"},{"name":"2University Cancer Center Schleswig-Holstein, Campus Kiel, Kiel, Germany"},{"name":"3Clinical Research Unit \u201cCATCH ALL\u201d (KFO 5010\/1), Kiel, 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