Related Experiment Video

Updated: Jan 29, 2026

Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma
08:53

Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma

Published on: June 10, 2017

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RHOA controls oncogenic B cell receptor signaling in aggressive lymphoma

Ariana N Jacobs1,2, Dominique Jahn2,3, Tim Beringer1,2

  • 1Department of Medicine 2, Hematology/Oncology, University Medical Center Frankfurt, Goethe University, Frankfurt am Main 60590, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|January 27, 2026
PubMed

Insights

RHOA protein is crucial for diffuse large B cell lymphoma (DLBCL) cell survival by sustaining B cell receptor (BCR) signaling. Mutations in RHOA can amplify this signaling, leading to treatment resistance in DLBCL.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Diffuse large B cell lymphoma (DLBCL) exhibits diverse genetic alterations influencing signaling pathways and treatment responses.
  • Identifying specific genetic dependencies is key to understanding DLBCL pathogenesis and developing targeted therapies.

Purpose of the Study:

  • To investigate the role of the small GTPase RHOA as a selective dependency in DLBCL.
  • To elucidate the mechanisms by which RHOA regulates oncogenic B cell receptor (BCR) signaling in ABC DLBCL cells.

Main Methods:

  • Analysis of recurrently mutated genes in DLBCL.
  • Functional studies assessing RHOA's impact on cell survival and signaling pathways.
  • Investigation of RHOA's role in actin network conformation and BCR microcluster formation.
  • Characterization of the RHOA R5W mutation's effects on RHOA activity and BCR signaling.

Main Results:

  • RHOA is essential for ABC DLBCL cell survival by sustaining BCR signaling via regulation of the cortical actin network.
  • RHOA controls BCR endocytosis and the assembly of the My-T-BCR complex, a key activator of NF-κB signaling.
  • The DLBCL-associated RHOA R5W mutation leads to constitutive RHOA activity, altered actin conformation, increased BCR signaling, and resistance to targeted inhibitors.

Conclusions:

  • RHOA is a critical regulator of oncogenic BCR signaling in DLBCL.
  • RHOA and its mutant isoforms represent potential therapeutic targets for DLBCL treatment.
  • Understanding RHOA's function provides insights into DLBCL dependencies and resistance mechanisms.
Keywords:
B cell receptorDLBCLRHOAcytoskeletonlymphoma

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