Journal Article

DKFZ-2026-00132

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Axes of biological variation in diffuse large B cell lymphoma.

Wang, B. ; Wright, G. ; Enssle, J. C.DKFZ* ; Yu, X. ; Phelan, J. D. ; Yang, Y. ; Shaffer, A. ; Ruiz, A. E. ; Huang, D. W. ; Coulibaly, Z. ; Kelly, M. ; Tran, B. ; Pittaluga, S. ; Roschewski, M. ; Wilson, W. H. ; Oellerich, T.DKFZ* ; Inghirami, G. ; Staudt, L. M.

2026
Cell Press Cambridge, Mass.

Abstract: Genetic and gene expression subtypes of diffuse large B cell lymphoma (DLBCL) have been defined using bulk tumor analysis. To explore their biology, we derived single-cell RNA and ATAC sequencing data from 103 DLBCL biopsies and identified malignant B cells by their non-diploid DNA copy number profiles. Using malignant B cell gene expression, we developed and validated signatures of each DLBCL genetic subtype, revealing their distinctive characters. Most biopsies had genetic subclones, defined by distinct patterns of aneuploidy, that were distinguished by expression of biological themes reflecting B cell differentiation state, cell proliferation, and cell growth. This analysis revealed REL amplification as a mechanism to block terminal memory B cell differentiation. The genetic subtype signatures and biological themes varied independently, had distinctive transcription factor networks, and were associated with survival following chemotherapy. This single-cell resource illuminates intra- and inter-tumoral biological variation, facilitating studies of DLBCL pathogenesis and therapeutic response.

Keyword(s): ATAC ; DLBCL genetic subtype ; RNA ; TF eRegulon ; genetic subclones ; single-cell analysis ; tumor microenvironment

Note: #DKTKZFB26# / 2026 Mar 9;44(3):567-585.e12

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Frankfurt (FM01)
2. DKTK FM Proteomics Facility (FM03)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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