Back to Search Start Over

Pediatric T-cell lymphoblastic lymphomas but not leukemias harbor TRB::NOTCH1 fusions with unfavorable outcome.

Authors :
Te Vrugt M
Wessolowski J
Randau G
Alfert A
Mueller S
Scholten K
Sopalla C
Lanvers-Kaminsky C
Hotfilder M
Lamp F
Damm-Welk C
Luedersen J
Escherich G
Zur Stadt U
Behrmann L
Woessmann W
Oschlies I
Marzi M
Zimmermann M
Burkhardt B
Source :
Blood [Blood] 2024 Sep 26; Vol. 144 (13), pp. 1412-1417.
Publication Year :
2024

Abstract

Abstract: T-cell lymphoblastic lymphoma (T-LBL) and T-cell acute lymphoblastic leukemia (T-ALL) have common and distinguishing clinical and molecular features. Molecular prognostic factors are needed for T-LBL. We assessed the prevalence and prognostic impact of the T-cell receptor β (TRB)::NOTCH1 fusion in 192 pediatric patients with T-LBL and 167 pediatric patients with T-ALL, using novel multiplex polymerase chain reaction and genomic capture high-throughput sequencing techniques. The fusion was detected in 12 patients with T-LBL (6.3%) but in none of the patients with T-ALL (P = .0006, Fisher exact test). In T-LBL, the TRB::NOTCH1 fusion was associated with a significantly higher incidence of relapse (67% vs 17% in gene fusion-negative patients, P < .001, Fisher exact test). The breakpoint in TRB was most frequently located in J2-7 (n = 6). In NOTCH1, the breakpoints varied between exon 24 and 27. Consequently, a truncated NOTCH1 with its dimerization, regulation, and signal transduction domains gets controlled by strong TRB enhancer elements. This study reveals a novel recurrent genetic variant with significant prognostic relevance in T-LBL, which was absent in T-ALL. The TRB::NOTCH1 fusion in T-LBL suggests a possible unique pathogenic mechanism divergent from T-ALL. Further studies will validate the role of the TRB::NOTCH1 fusion as prognostic marker in T-LBL and elucidate its pathogenic mechanisms.<br /> (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Details

Language :
English
ISSN :
1528-0020
Volume :
144
Issue :
13
Database :
MEDLINE
Journal :
Blood
Publication Type :
Academic Journal
Accession number :
39024510
Full Text :
https://doi.org/10.1182/blood.2024025307