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

被引：24

作者：

Broseus, Julien ^{[1
,2
,3
]}

Hergalant, Sebastien ^{[2
]}

Vogt, Julia ^{[4
]}

Tausch, Eugen ^{[1
]}

Kreuz, Markus ^{[5
]}

Mottok, Anja ^{[4
]}

Schneider, Christof ^{[1
]}

Dartigeas, Caroline ^{[6
]}

Roos-Weil, Damien ^{[7
]}

Quinquenel, Anne ^{[8
]}

Moulin, Charline ^{[9
,10
]}

Ott, German ^{[11
]}

Blanchet, Odile ^{[12
,21
]}

Tomowiak, Cecile ^{[13
,14
]}

Lazarian, Gregory H.

Rouyer, Pierre ^{[2
]}

Chteinberg, Emil ^{[4
]}

Bernhart, Stephan ^{[16
]}

Tournilhac, Olivier ^{[17
]}

Gauchotte, Guillaume ^{[2
,18
]}

Lomazzi, Sandra ^{[19
,23
]}

Chapiro, Elise ^{[20
,23
]}

Nguyen-Khac, Florence ^{[15
,20
,22
]}

Chery, Celine ^{[2
,21
,22
]}

Davi, Frederic

Hunault, Mathilde ^{[24
]}

Houlgatte, Remi ^{[2
]}

Rosenwald, Andreas ^{[25
]}

Delmer, Alain ^{[8
]}

Meyre, David ^{[2
]}

Bene, Marie-Christine ^{[26
,27
]}

Thieblemont, Catherine ^{[28
]}

Lichter, Peter ^{[29
,30
]}

Ammerpohl, Ole ^{[4
]}

Gueant, Jean-Louis ^{[2
]}

Guieze, Romain ^{[17
]}

Martin-Subero, Jose Ignacio ^{[31
,32
]}

Cymbalista, Florence

Feugier, Pierre ^{[2
,9
]}

Siebert, Reiner ^{[4
]}

Stilgenbauer, Stephan ^{[1
]}

机构：

[1] Ulm Univ, Dept Internal Med 3, Div CLL, Ulm, Germany

[2] Univ Lorraine, Inserm Nutr Genet & Exposit Risques Environnm N GE, Nancy, France

[3] Univ Lorraine, CHRU Nancy, Serv Hematol Biol, Pole Labs, F-54000 Nancy, France

[4] Ulm Univ, Inst Human Genet, Ulm, Germany

[5] Fraunhofer Inst Cell Therapy & Immunol IZI, Leipzig, Germany

[6] Univ Hosp Tours, Dept Haematol, Tours, France

[7] Hop La Pitie Salpetriere, Dept Hematol, AP HP, Paris, France

[8] Univ Reims, Ctr Hosp Univ Reims, IRMAIC, Hematol Clin,IRMAIC, Reims, France

[9] Univ Hosp Nancy, Dept Hematol, Nancy, France

[10] Univ Lorraine, Inserm, CHRU, Clin Epidemiol CIC, Nancy, France

[11] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany

[12] CHU Angers, Biol Resource Ctr Angers CRB CHU Angers, Lab dHematol, Angers, France

[13] CHU Poitiers, Dept Hematol, Poitiers, France

[14] CIC1402 Inserm Poitiers, Poitiers, France

[15] Avicenne Hosp, Assistance Publ Hop Paris, Hematol Lab, Paris, France

[16] Univ Leipzig, Interdisciplinary Ctr Bioinformat, Dept Comp Sci, Bioinformat Grp, Leipzig, Germany

[17] Clermont Ferrand Univ Hosp, Hematol Dept, Clermont Ferrand, France

[18] CHRU Nancy, Dept Biopathol, CHRU ICL, BBB, Vandoeuvre Les Nancy, France

[19] CHRU Nancy, Biol Resource Ctr Nancy, F-00035 Nancy, France

[20] Sorbonne Univ, Hop Pitie Salpetriere, Cytogenet Hematol, AP HP, Paris, France

[21] Univ Paris Diderot, Univ Sorbonne Paris Cite, Univ Paris Descartes, Ctr Rech Cordeliers,INSERM, F-75006 Paris, France

[22] CHRU Nancy, Serv Biochim Biol Mol Nutr, Pole Labs, F-54000 Nancy, France

[23] Sorbonne Univ, Hop Pitie Salpetriere, AP HP, Hematol Dept, Paris, France

[24] Univ Hosp Angers, Dept Hematol, Angers, France

[25] Univ Hosp Wurzburg, Inst Pathol, Bavaria, Germany

[26] Univ Hosp Nantes, Hematol Biol, Hotel Dieu, France

[27] Ctr Rech Cancerol & Immunol Nantes Angers CRCINA, Inserm 1232, Nantes, France

[28] Hop St Louis, Dept Hematol, Paris, France

[29] German Canc Consortium DKTK, Div Mol Genet, Heidelberg, Germany

[30] German Canc Res Ctr, Natl Ctr Tumor Dis NCT Heidelberg, Heidelberg, Germany

[31] Univ Barcelona, Inst Invest Biomed August PiSunyer IDIBAPS 1, Biomed Epigen Grp, Barcelona, Spain

[32] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

关键词：

CHRONIC-LYMPHOCYTIC-LEUKEMIA; DIFFERENTIALLY METHYLATED REGIONS; DNA METHYLATION; R/BIOCONDUCTOR PACKAGE; TRANSFORMATION; SUBGROUPS; METHYLOME; SIGNATURE; PATHWAYS; DEFINES;

D O I：

10.1038/s41467-022-34642-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Richter syndrome (RS) is the transformation of chronic lymphocytic leukaemia (CLL) into aggressive lymphoma, in most cases diffuse large B-cell lymphoma (DLBCL). Here, the authors characterize the DNA methylation and transcriptomic profiles of RS samples, find a clonally-related CLL epigenetic imprint, and develop classifiers for "RS-type" de novo DLBCLs. 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.

引用

页数：19

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