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Pediatric T-cell lymphoblastic lymphomas but not leukemias harbor TRB::NOTCH1 fusions with unfavorable outcome.
- 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.)
- Subjects :
- Humans
Child
Male
Female
Adolescent
Child, Preschool
Prognosis
Infant
Receptor, Notch1 genetics
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma pathology
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma mortality
Oncogene Proteins, Fusion genetics
Subjects
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