CD79B – Diffuse large B-cell lymphoma

CD79B encodes the immunoglobulin-β (Igβ) signaling subunit of the B-cell receptor complex, and somatic mutations in CD79B are recurrently observed in diffuse large B-cell lymphoma (Diffuse large B-cell lymphoma). These variants cluster in the immunoreceptor tyrosine-based activation motif (ITAM) and potentiate NF-κB pathway activation, underpinning the pathogenic basis for targeted therapies.

Genetic studies in diverse DLBCL cohorts demonstrate CD79B mutation frequencies ranging from 8.5% (16/187 nodal cases) (PMID:24444466) to 61.1% (11/18 primary CNS DLBCLs) (PMID:25347427). A meta-analysis of nine studies encompassing over 2,300 patients confirms that CD79B-mutant DLBCL exhibits inferior overall survival (HR 1.38; 95% CI 1.13–1.70; p=0.0021) independent of International Prognostic Index variables (PMID:36182550).

The variant spectrum is dominated by missense substitutions affecting the ITAM tyrosine 196 codon (Y196C/D/H/A), exemplified by c.586T>G (p.Tyr196Asp), which disrupts signal attenuation and sustains BCR signaling.

Functional assays indicate that CD79B Y196 mutants form constitutive signaling complexes with MYD88, MALT1, and BTK, driving NF-κB activation. In an autochthonous murine DLBCL model, Cd79b ITAM mutations on a Myd88-driven background confer heightened sensitivity to the BTK inhibitor ibrutinib, validating CD79B as a therapeutic biomarker (PMID:38060829).

Ethnic variation is noted: in an Indian de novo nodal DLBCL cohort (n=30), CD79B and CARD11 mutations were absent, underscoring population-specific mutational landscapes (PMID:29734251).

No studies to date have refuted the association between CD79B ITAM mutations and DLBCL pathogenesis; rather, concordant genetic and experimental data reinforce a model of chronic BCR-NF-κB signaling in this lymphoma subset.

Integration of these findings supports CD79B mutation screening as a diagnostic and prognostic tool and guides the use of BTK inhibitors in CD79B-mutant DLBCL. Key take-home: CD79B ITAM mutations define a molecular subtype of DLBCL with actionable NF-κB dependence and adverse prognosis.

References

• Human pathology • 2014 • CD79B and MYD88 mutations in diffuse large B-cell lymphoma. PMID:24444466
• Leukemia & lymphoma • 2015 • Primary diffuse large B-cell lymphomas of central nervous system exhibit remarkably high prevalence of oncogenic MYD88 and CD79B mutations. PMID:25347427
• Clinical lymphoma, myeloma & leukemia • 2022 • The Prognostic Significance of CD79B Mutation in Diffuse Large B-Cell Lymphoma: A Meta-analysis and Systematic Literature Review. PMID:36182550
• Applied immunohistochemistry & molecular morphology • 2019 • MYD88, CARD11, and CD79B Oncogenic Mutations are Rare Events in the Indian Cohort of De Novo Nodal Diffuse Large B-Cell Lymphoma. PMID:29734251
• Blood advances • 2024 • An inducible Cd79b mutation confers ibrutinib sensitivity in mouse models of Myd88-driven diffuse large B-cell lymphoma. PMID:38060829

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