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  1. Home
  2. Pathogenesis Of Diffuse Large B Cell Lymphoma Proteogenotypes.
  1. Home
  2. Pathogenesis Of Diffuse Large B Cell Lymphoma Proteogenotypes.

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Published on: February 12, 2022

Pathogenesis of diffuse large B cell lymphoma proteogenotypes.

Julius C Enssle1, Björn Häupl2, Arber Qoku3

  • 1Department of Medicine, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, a Partnership Between DKFZ and UCT Frankfurt-Marburg, Germany, Frankfurt am Main, Germany; Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Cancer Cell
|June 4, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

Researchers identified seven diffuse large B cell lymphoma (DLBCL) proteogenotypes (PGs). PG4 is linked to poor outcomes, regardless of other factors, and reveals common oncogenic pathways for targeted therapies.

Keywords:
B cell receptorMYCgenomicsimmune exhaustionlymphomamulti-omics data integrationprotein translationproteomicssingle cell sequencingtumor microenvironment

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Area of Science:

  • Oncology
  • Genomics
  • Proteomics

Background:

  • Diffuse large B cell lymphoma (DLBCL) exhibits significant clinical and molecular heterogeneity.
  • Current understanding of DLBCL subtypes and their underlying biology remains incomplete.

Purpose of the Study:

  • To integrate multi-omic data for a deeper understanding of DLBCL heterogeneity.
  • To identify novel molecular subgroups and their clinical implications.
  • To establish a proteogenomic framework for DLBCL classification and treatment.

Main Methods:

  • Integrated analysis of proteomic, transcriptomic, and genomic data from 478 DLBCL tumors.
  • Proteogenomic profiling to define distinct DLBCL subgroups (proteogenotypes).
  • Single-cell sequencing and spatial transcriptomics to investigate cellular phenotypes and microenvironment.

Main Results:

  • Identified seven distinct DLBCL proteogenotypes (PGs) that encompass known molecular subtypes.
  • PG4 emerged as a high-risk subgroup associated with poor outcomes, independent of existing prognostic factors.
  • PG4 tumors exhibit a dark-zone B cell phenotype, enriched BTG1 mutations, activated MYC and TCF3/4 signaling, and an exhausted CD8+ T cell microenvironment.

Conclusions:

  • Proteogenomic profiling provides a refined classification of DLBCL.
  • PG4 represents a high-risk DLBCL subgroup with distinct molecular drivers and microenvironment characteristics.
  • This study offers a foundation for developing novel diagnostic and therapeutic strategies for aggressive DLBCL.