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December 8, 2025BloodOpen Access

Autonomous BCR signaling and the CARD11 L251P mutation as alternative oncogenic drivers induce identical gene expression profiles in genetically engineered ABC-DLBCL models

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Authors

CBCornelis A.M. van BergenHVHendrik Veelken

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Overview

Reciprocal genetic engineering reveals distinct gene expression profiles driven by BCR signaling and CARD11 mutation in ABC-DLBCL.

Key Points

  • This study explores the transcriptional consequences of autonomous BCR signaling and the CARD11 L251P mutation in ABC-DLBCL models.
  • Utilized reciprocal genetic engineering of ABC-DLBCL cell lines TMD8 and OCI-Ly3
  • Established various genetically modified clones through gene editing and retroviral transduction
  • Performed RNA sequencing and differential gene expression analyses on the clones.
  • Identified 3904 differentially expressed genes in TMD8 clones and 1081 in OCI-Ly3 clones after exchanging drivers.
  • Only 216 genes were differentially expressed in both systems, indicating limited overlap.
  • CD69 and CXCR4 were upregulated by autonomous BCR signaling; CCND2 was associated with CARD11L251P.

Cite This Study

Bergen et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dcd3https://doi.org/10.1182/blood-2025-1484
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Abstract 6986: Oncogenic CARD11 enhances marginal zone B cell survival by potentiating the non-canonical NF-κB pathway2024
  2. 2Antigen-independent, autonomous B cell receptor signaling drives activated B cell DLBCL2024 · 19 citations
  3. 3Inhibition of autoantigen-induced B-cell receptor (BCR) internalization as a therapeutic strategy in diffuse large B cell lymphoma (DLBCL)2026
  4. 4Integrated single-cell and bulk transcriptomic analyses reveal cellular and molecular mechanisms of ABC-type DLBCL progression and prognosis2026
  5. 5Inhibition of autoantigen-induced B-cell receptor (BCR) internalization as a therapeutic strategy in Diffuse Large B Cell Lymphoma (DLBCL)2025