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Article Dans Une Revue Nature Communications Année : 2023

Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis

1 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
2 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
3 Universität Ulm - Ulm University [Ulm, Allemagne]
4 Universitätsklinikum Ulm - University Hospital of Ulm
5 Fraunhofer IZI - Fraunhofer Institute for Cell Therapy and Immunology
6 Service d'hématologie [Tours]
7 CHU Pitié-Salpêtrière [AP-HP]
8 IRMAIC - Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509
9 Service d'Hématologie [CHRU Nancy]
10 CIC-EC - Centre d'investigation clinique - Epidémiologie clinique [Nancy]
11 Robert-Bosch-Krankenhaus
12 Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart]
13 CHU Angers - Centre Hospitalier Universitaire d'Angers
14 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
15 CIC 1402 - CIC Poitiers – Centre d'investigation clinique de Poitiers
16 Service d'hématologie biologique [Avicenne]
17 IZBI - Interdisciplinary Centre for Bioinformatics [Leipzig]
18 Service d’Hématologie Biologique [CHU Clermont-Ferrand]
19 CRB Nancy - Centre de Ressources Biologiques - [Nancy]
20 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
21 Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy]
22 Service d'hématologie [Angers]
23 University Hospital Wuerzburg / Universitäts­klinikum Würzburg
24 CHU Nantes - Centre Hospitalier Universitaire de Nantes
25 CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
26 Service d'Hémato-oncologie [CHU Saint-Louis]
27 DKTK - German Cancer Consortium [Heidelberg]
28 NCT / DKFZ - National Center for Tumor Diseases - Deutsches Krebsforschungszentrum [Heidelberg, Allemagne]
29 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
30 ICREA - Institució Catalana de Recerca i Estudis Avançats = Catalan Institution for Research and Advanced Studies
Stephan Stilgenbauer

Résumé

Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). We characterize 58 primary human RS samples by genome-wide DNA methylation and whole-transcriptome profiling. Our comprehensive approach determines RS DNA methylation profile and unravels a CLL epigenetic imprint, allowing CLL-RS clonal relationship assessment without the need of the initial CLL tumor DNA. DNA methylation - and transcriptomic-based classifiers were developed, and testing on landmark DLBCL datasets identifies a poor-prognosis, activated B-cell-like DLBCL subset in 111/1772 samples. The classification robustly identifies phenotypes very similar to RS with a specific genomic profile, accounting for 4.3-8.3% of de novo DLBCLs. In this work, RS multi-omics characterization determines oncogenic mechanisms, establishes a surrogate marker for CLL-RS clonal relationship, and provides a clinically relevant classifier for a subset of primary “RS-type DLBCL” with unfavorable prognosis.
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Dates et versions

hal-03950368 , version 1 (23-01-2023)

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Julien Broséus, Sébastien Hergalant, Julia Vogt, Eugen Tausch, Markus Kreuz, et al.. Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis. Nature Communications, 2023, 14 (1), pp.309. ⟨10.1038/s41467-022-34642-6⟩. ⟨hal-03950368⟩
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