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

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Integrative genomic analysis of pediatric T- cell lymphoblastic lymphoma reveals candidates of clinical significance. / Khanam, Tasneem; Sandmann, Sarah; Seggewiss, Jochen; Ruether, Charlotte Marie; Zimmermann, Martin; Norvil, Allison B; Bartenhagen, Christoph; Randau, Gerrit; Mueller, Stephanie; Herbrüggen, Heidrun; Hoffmann, Per; Herms, Stefan; Wei, Lanying; Wöste, Marius; Wünsch, Christian; Gowher, Humaira; Oschlies, Ilske; Klapper, Wolfram; Woessmann, Wilhelm; Dugas, Martin; Burkhardt, Birgit.

in: BLOOD, Jahrgang 137, Nr. 17, 29.04.2021, S. 2347-2359.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Khanam, T, Sandmann, S, Seggewiss, J, Ruether, CM, Zimmermann, M, Norvil, AB, Bartenhagen, C, Randau, G, Mueller, S, Herbrüggen, H, Hoffmann, P, Herms, S, Wei, L, Wöste, M, Wünsch, C, Gowher, H, Oschlies, I, Klapper, W, Woessmann, W, Dugas, M & Burkhardt, B 2021, 'Integrative genomic analysis of pediatric T- cell lymphoblastic lymphoma reveals candidates of clinical significance', BLOOD, Jg. 137, Nr. 17, S. 2347-2359. https://doi.org/10.1182/blood.2020005381

APA

Khanam, T., Sandmann, S., Seggewiss, J., Ruether, C. M., Zimmermann, M., Norvil, A. B., Bartenhagen, C., Randau, G., Mueller, S., Herbrüggen, H., Hoffmann, P., Herms, S., Wei, L., Wöste, M., Wünsch, C., Gowher, H., Oschlies, I., Klapper, W., Woessmann, W., ... 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

Vancouver

Khanam T, Sandmann S, Seggewiss J, Ruether CM, Zimmermann M, Norvil AB et al. Integrative genomic analysis of pediatric T- cell lymphoblastic lymphoma reveals candidates of clinical significance. BLOOD. 2021 Apr 29;137(17):2347-2359. https://doi.org/10.1182/blood.2020005381

Bibtex

@article{dcef403d37bd4f14b07e2d066dc5933b,
title = "Integrative genomic analysis of pediatric T- cell lymphoblastic lymphoma reveals candidates of clinical significance",
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.",
author = "Tasneem Khanam and Sarah Sandmann and Jochen Seggewiss and Ruether, {Charlotte Marie} and Martin Zimmermann and Norvil, {Allison B} and Christoph Bartenhagen and Gerrit Randau and Stephanie Mueller and Heidrun Herbr{\"u}ggen and Per Hoffmann and Stefan Herms and Lanying Wei and Marius W{\"o}ste and Christian W{\"u}nsch and Humaira Gowher and Ilske Oschlies and Wolfram Klapper and Wilhelm Woessmann and Martin Dugas and Birgit Burkhardt",
note = "Copyright {\textcopyright} 2020 American Society of Hematology.",
year = "2021",
month = apr,
day = "29",
doi = "10.1182/blood.2020005381",
language = "English",
volume = "137",
pages = "2347--2359",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "17",

}

RIS

TY - JOUR

T1 - Integrative genomic analysis of pediatric T- cell lymphoblastic lymphoma reveals candidates of clinical significance

AU - Khanam, Tasneem

AU - Sandmann, Sarah

AU - Seggewiss, Jochen

AU - Ruether, Charlotte Marie

AU - Zimmermann, Martin

AU - Norvil, Allison B

AU - Bartenhagen, Christoph

AU - Randau, Gerrit

AU - Mueller, Stephanie

AU - Herbrüggen, Heidrun

AU - Hoffmann, Per

AU - Herms, Stefan

AU - Wei, Lanying

AU - Wöste, Marius

AU - Wünsch, Christian

AU - Gowher, Humaira

AU - Oschlies, Ilske

AU - Klapper, Wolfram

AU - Woessmann, Wilhelm

AU - Dugas, Martin

AU - Burkhardt, Birgit

N1 - Copyright © 2020 American Society of Hematology.

PY - 2021/4/29

Y1 - 2021/4/29

N2 - 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.

AB - 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.

U2 - 10.1182/blood.2020005381

DO - 10.1182/blood.2020005381

M3 - SCORING: Journal article

C2 - 33152759

VL - 137

SP - 2347

EP - 2359

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 17

ER -