CARD9 Forms an Alternative CBM Complex in Richter Syndrome.
Julia Maier1, André Lechel2, Ralf Marienfeld1
1Institute of Pathology, University Hospital Ulm, 89081 Ulm, Germany.
Cancers
|February 15, 2022
Summary
Richter syndrome (RS), a transformation of chronic lymphocytic leukemia (CLL), involves aggressive lymphoma. Researchers found CARD9 protein and mRNA in RS cells, activating NF-κB signaling and impacting cell viability.
Area of Science:
- Molecular Biology
- Oncology
- Immunology
Background:
- Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into aggressive lymphoma, often diffuse large B-cell lymphoma (DLBCL).
- The pathobiology of Richter transformation remains incompletely understood.
- Patients with RS have a poor prognosis despite treatment.
Purpose of the Study:
- To investigate the molecular mechanisms underlying Richter syndrome pathogenesis.
- To identify novel molecular players in the transformation of CLL to DLBCL.
- To explore the role of CARD9 in the aggressive B-cell lymphoma of RS.
Main Methods:
- Analysis of mRNA and protein levels of CARD9 in the RS cell line U-RT1.
- Co-immunoprecipitation to assess CBM complex formation.
- Western blot analysis to evaluate NF-κB pathway activation (IκB, IKK phosphorylation).
- siRNA knockdown of CARD9 to assess its functional impact on cell viability and CYLD cleavage.
- Immunostaining of CARD9 in RS tissue specimens and other lymphomas.
Main Results:
- High mRNA and protein levels of CARD9 were detected in the U-RT1 RS cell line.
- A CBM complex assembled using CARD9, not CARD11, was identified.
- Constitutive activation of the canonical NF-κB pathway was observed in U-RT1 cells.
- CARD9 knockdown significantly reduced U-RT1 cell viability and affected CYLD cleavage.
- CARD9 expression was found in 53% of RS tissue specimens, with rare expression in other lymphomas.
Conclusions:
- This study reports the ectopic expression and function of CARD9 in aggressive B-cell lymphoma for the first time.
- CARD9 activates the NF-κB pathway in the context of Richter syndrome.
- CARD9 may play a significant role in the pathogenesis of Richter syndrome.
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