Universität zu Köln

Khanam, Tasneem, Sandmann, Sarah ORCID: 0000-0002-5011-0641, Seggewiss, Jochen, Ruether, Charlotte, Zimmermann, Martin, Norvil, Allison B., Bartenhagen, Christoph, Randau, Gerrit, Mueller, Stephanie, Herbrueggen, Heidi, Hoffmann, Per, Herms, Stefan, Wei, Lanying, Woeste, Marius, Wuensch, Christian, Gowher, Humaira, Oschlies, Ilske, Klapper, Wolfram, Woessmann, Wilhelm, Dugas, Martin and Burkhardt, Birgit ORCID: 0000-0002-1151-829X (2021). Integrative genomic analysis of pediatric T-cell lymphoblastic lymphoma reveals candidates of clinical significance. Blood, 137 (17). S. 2347 - 2360. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Khanam, Tasneem UNSPECIFIED UNSPECIFIED UNSPECIFIED Sandmann, Sarah UNSPECIFIED orcid.org/0000-0002-5011-0641 UNSPECIFIED Seggewiss, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruether, Charlotte UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmermann, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Norvil, Allison B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartenhagen, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Randau, Gerrit UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Herbrueggen, Heidi UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Per UNSPECIFIED UNSPECIFIED UNSPECIFIED Herms, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wei, Lanying UNSPECIFIED UNSPECIFIED UNSPECIFIED Woeste, Marius UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuensch, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Gowher, Humaira UNSPECIFIED UNSPECIFIED UNSPECIFIED Oschlies, Ilske UNSPECIFIED UNSPECIFIED UNSPECIFIED Klapper, Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Woessmann, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Dugas, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Burkhardt, Birgit UNSPECIFIED orcid.org/0000-0002-1151-829X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-599638
DOI:	10.1182/blood.2020005381
Journal or Publication Title:	Blood
Volume:	137
Number:	17
Page Range:	S. 2347 - 2360
Date:	2021
Publisher:	AMER SOC HEMATOLOGY
Place of Publication:	WASHINGTON
ISSN:	1528-0020
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION; NOTCH1 MUTATIONS; PROGNOSTIC RELEVANCE; DNA METHYLATION; FBXW7 MUTATIONS; BREAST-CANCER; MLL FAMILY; LEUKEMIA; PTEN; RESISTANCE Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59963