Integrative genomic analysis of pediatric T-cell lymphoblastic lymphoma reveals candidates of clinical significance

36Citations
Citations of this article
57Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

T-cell lymphoblastic lymphoma (T-LBL) is a heterogeneous malignancy of lymphoblasts committed to T-cell lineage. The dismal outcomes (15%-30%) after T-LBL relapse warrant establishing risk-based treatment. To our knowledge, this study presents the first comprehensive, systematic, integrated, genome-wide analysis including relapsed cases that identifies molecular markers of prognostic relevance for T-LBL. NOTCH1 was identified as the putative driver for T-LBL. An activated NOTCH/PI3K-AKT signaling axis and alterations in cell cycle regulators constitute the core oncogenic program for T-LBL. Mutated KMT2D was identified as a prognostic marker. The cumulative incidence of relapse was 47% ± 17% in patients with KMT2D mutations, compared with 14% ± 3% in wild-type KMT2D. Structural analysis of the mutated domains of KMT2D revealed a plausible impact on structure and functional consequences. These findings provide new insights into the pathogenesis of T-LBL, including high translational potential. The ongoing LBL 2018 trial (www.clinicaltrials.gov #NCT04043494) allows for prospective validation and subsequent fine tuning of the stratification criteria for T-LBL risk groups to improve survival of pediatric patients.

Cite

CITATION STYLE

APA

Khanam, T., Sandmann, S., Seggewiss, J., Ruether, C., Zimmermann, M., Norvil, A. B., … Burkhardt, B. (2021). Integrative genomic analysis of pediatric T-cell lymphoblastic lymphoma reveals candidates of clinical significance. Blood, 137(17), 2347–2359. https://doi.org/10.1182/blood.2020005381

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free