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NGS-based IG/TR gene rearrangement profiling in acute lymphoblastic leukemia: age dependence of immunogenetic maturation

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 decreas...

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Hauptverfasser: Kotrová, Michaela (VerfasserIn) , Proske, Constantin (VerfasserIn) , Darzentas, Nikos (VerfasserIn) , Laqua, Anna (VerfasserIn) , Kehden, Britta (VerfasserIn) , Kässens, Jan (VerfasserIn) , Bendig, Sonja (VerfasserIn) , Kohlscheen, Saskia (VerfasserIn) , Szczepanowski, Monika (VerfasserIn) , Wessels, Wiebke (VerfasserIn) , Antic, Željko (VerfasserIn) , Pott, Christiane (VerfasserIn) , Ritgen, Matthias (VerfasserIn) , van Dongen, Jacques J. M. (VerfasserIn) , Gökbuget, Nicola (VerfasserIn) , Chitadze, Guranda (VerfasserIn) , Bergmann, Anke (VerfasserIn) , Bastian, Lorenz (VerfasserIn) , Baldus, Claudia D. (VerfasserIn) , Cario, Gunnar (VerfasserIn) , Schrappe, Martin (VerfasserIn) , Schwartz, Stefan (VerfasserIn) , Alten, Julia (VerfasserIn) , Köhler, Rolf (VerfasserIn) , Brüggemann, Monika (VerfasserIn)
Dokumenttyp: Article (Journal) Editorial
Sprache:Englisch
Veröffentlicht: 31 July 2025
In: Blood
Year: 2025, Jahrgang: 146, Heft: 5, Pages: 585-589
ISSN:1528-0020
DOI:10.1182/blood.2024027175
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1182/blood.2024027175
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0006497125007232
Volltext
Verfasserangaben:Michaela Kotrová, Constantin Proske, Nikos Darzentas, Anna Laqua, Britta Kehden, Jan Kässens, Sonja Bendig, Saskia Kohlscheen, Monika Szczepanowski, Wiebke Wessels, Željko Antic, Christiane Pott, Matthias Ritgen, Jacques J.M. van Dongen, Nicola Gökbuget, Guranda Chitadze, Anke Bergmann, Lorenz Bastian, Claudia D. Baldus, Gunnar Cario, Martin Schrappe, Stefan Schwartz, Julia Alten, Rolf Köhler, and Monika Brüggemann

MARC

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520 |a 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 κ rearrangements in B-ALL and complete TR β/δ rearrangements in T-ALL, hallmarks of maturity, were more frequent in pediatric patients compared to adults (B-ALL: 68.7% vs 39.0%, P < 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. 
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