Journal Article

DKFZ-2025-01605

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png NGS-based IG/TR gene rearrangement profiling in acute lymphoblastic leukemia: age dependence of immunogenetic maturation.

Kotrová, M. ; Proske, C. ; Darzentas, N. ; Laqua, A. ; Kehden, B. ; Kässens, J. ; Bendig, S. ; Kohlscheen, S. ; Szczepanowski, M. ; Wessels, W. ; Antic, Ž. ; Pott, C. ; Ritgen, M. ; van Dongen, J. J. M. ; Gökbuget, N. ; Chitadze, G. ; Bergmann, A. ; Bastian, L. ; Baldus, C. D. ; Cario, G. ; Schrappe, M. ; Schwartz, S.DKFZ* ; Alten, J. ; Köhler, R. ; Brüggemann, M.

2025
American Society of Hematology Washington, DC

Abstract: 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.

Keyword(s): Humans (MeSH) ; Child (MeSH) ; Child, Preschool (MeSH) ; Adolescent (MeSH) ; Precursor Cell Lymphoblastic Leukemia-Lymphoma: genetics (MeSH) ; Precursor Cell Lymphoblastic Leukemia-Lymphoma: immunology (MeSH) ; Male (MeSH) ; Female (MeSH) ; Adult (MeSH) ; High-Throughput Nucleotide Sequencing (MeSH) ; Infant (MeSH) ; Young Adult (MeSH) ; Middle Aged (MeSH) ; Age Factors (MeSH) ; Receptors, Antigen, T-Cell: genetics (MeSH) ; Aged (MeSH) ; Gene Rearrangement (MeSH) ; Gene Rearrangement, T-Lymphocyte (MeSH) ; Receptors, Antigen, T-Cell

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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