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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
19 01 2023
Historique:
received: 04 02 2022
accepted: 01 11 2022
entrez: 19 1 2023
pubmed: 20 1 2023
medline: 24 1 2023
Statut: epublish

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.

Identifiants

pubmed: 36658118
doi: 10.1038/s41467-022-34642-6
pii: 10.1038/s41467-022-34642-6
pmc: PMC9852595
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

309

Investigateurs

Stephan Bernhart (S)

Informations de copyright

© 2023. The Author(s).

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Auteurs

Julien Broséus (J)

Division of CLL. Department of Internal Medicine III, Ulm University, Ulm, Germany. julien.broseus@univ-lorraine.fr.
Inserm UMRS1256 Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Université de Lorraine, Nancy, France. julien.broseus@univ-lorraine.fr.
Université de Lorraine, CHRU-Nancy, Service d'Hématologie Biologique, Pôle Laboratoires, F54000, Nancy, France. julien.broseus@univ-lorraine.fr.

Sébastien Hergalant (S)

Inserm UMRS1256 Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Université de Lorraine, Nancy, France.

Julia Vogt (J)

Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany.

Eugen Tausch (E)

Division of CLL. Department of Internal Medicine III, Ulm University, Ulm, Germany.

Markus Kreuz (M)

Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany.

Anja Mottok (A)

Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany.

Christof Schneider (C)

Division of CLL. Department of Internal Medicine III, Ulm University, Ulm, Germany.

Caroline Dartigeas (C)

Department of Haematology, University Hospital of Tours, Tours, France.

Damien Roos-Weil (D)

Department of Hematology, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France.

Anne Quinquenel (A)

Université de Reims Champagne-Ardenne, IRMAIC, Centre Hospitalier Universitaire de Reims, Hématologie Clinique, Reims, France.

Charline Moulin (C)

Department of Hematology, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.
Inserm, CHRU, University of Lorraine, CIC Clinical Epidemiology, Nancy, France.

German Ott (G)

Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, Germany.

Odile Blanchet (O)

CHU Angers, Biological Resource Center of Angers (CRB-CHU Angers), BB-0033-00038, Laboratoire d'Hématologie, Angers, France.

Cécile Tomowiak (C)

Department of Hematology, CHU Poitiers, Poitiers, France.
CIC1402 Inserm Poitiers, Poitiers, France.

Grégory Lazarian (G)

Hematology Laboratory, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Pierre Rouyer (P)

Inserm UMRS1256 Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Université de Lorraine, Nancy, France.

Emil Chteinberg (E)

Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany.

Stephan H Bernhart (SH)

Bioinformatics Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, Leipzig University, Leipzig, Germany.

Olivier Tournilhac (O)

Hematology department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.

Guillaume Gauchotte (G)

Inserm UMRS1256 Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Université de Lorraine, Nancy, France.
Department of Biopathology CHRU-ICL, BBB, CHRU Nancy, Vandoeuvre-lès-Nancy, France.

Sandra Lomazzi (S)

Biological Resource Center of Nancy, BB-0033-00035, CHRU de Nancy, Nancy, France.

Elise Chapiro (E)

Sorbonne Université, Cytogénétique Hématologique, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France.
Centre de Recherche des Cordeliers, INSERM, Université Sorbonne Paris Cite, Université Paris Descartes, Université Paris Diderot, F-75006, Paris, France.

Florence Nguyen-Khac (F)

Sorbonne Université, Cytogénétique Hématologique, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France.
Centre de Recherche des Cordeliers, INSERM, Université Sorbonne Paris Cite, Université Paris Descartes, Université Paris Diderot, F-75006, Paris, France.

Céline Chery (C)

Inserm UMRS1256 Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Université de Lorraine, Nancy, France.
CHRU of Nancy, Service de Biochimie-Biologie Moléculaire-Nutrition, Pôle Laboratoires, F54000, Nancy, France.

Frédéric Davi (F)

Centre de Recherche des Cordeliers, INSERM, Université Sorbonne Paris Cite, Université Paris Descartes, Université Paris Diderot, F-75006, Paris, France.
Hematology Department, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne University, Paris, France.

Mathilde Hunault (M)

Department of Hematology, University Hospital of Angers, Angers, France.

Rémi Houlgatte (R)

Inserm UMRS1256 Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Université de Lorraine, Nancy, France.

Andreas Rosenwald (A)

Institute of Pathology, University Hospital of Würzburg, Bavaria, Germany.

Alain Delmer (A)

Université de Reims Champagne-Ardenne, IRMAIC, Centre Hospitalier Universitaire de Reims, Hématologie Clinique, Reims, France.

David Meyre (D)

Inserm UMRS1256 Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Université de Lorraine, Nancy, France.

Marie-Christine Béné (MC)

Hematology Biology, University Hospital of Nantes, Hôtel-Dieu, France.
Inserm 1232 Centre de Recherche en Cancérologie et Immunologie Nantes Angers (CRCINA), Nantes, France.

Catherine Thieblemont (C)

Department of Hematology, Hôpital Saint-Louis, Paris, France.

Peter Lichter (P)

Division of Molecular Genetics, German Cancer Consortium (DKTK) and National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Ole Ammerpohl (O)

Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany.

Jean-Louis Guéant (JL)

Inserm UMRS1256 Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Université de Lorraine, Nancy, France.
CHRU of Nancy, Service de Biochimie-Biologie Moléculaire-Nutrition, Pôle Laboratoires, F54000, Nancy, France.

Romain Guièze (R)

Hematology department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.

José Ignacio Martin-Subero (JI)

Biomedical Epigenomics Group, Institut d'investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.

Florence Cymbalista (F)

Hematology Laboratory, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Pierre Feugier (P)

Inserm UMRS1256 Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Université de Lorraine, Nancy, France.
Department of Hematology, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.

Reiner Siebert (R)

Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany.

Stephan Stilgenbauer (S)

Division of CLL. Department of Internal Medicine III, Ulm University, Ulm, Germany. Stephan.Stilgenbauer@uniklinik-ulm.de.

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