Differential role of CREBBP missense and truncating mutations in germinal center development and lymphomagenesis - PubMed
6 hours ago
- #germinal center
- #lymphomagenesis
- #CREBBP mutations
- CREBBP gene mutations (truncating and missense) are common in follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL).
- Missense mutations (e.g., CREBBP-R1446H) and truncating mutations have distinct effects on germinal center (GC) development and lymphomagenesis.
- CREBBP-R1446H mutation leads to abnormal GC architecture, increased Tfh cells, and skewed immune response toward memory B-cell differentiation.
- Missense mutations like CREBBP-R1446H have stronger tumor-promoting activity compared to complete CREBBP loss.
- Lymphoma cells with CREBBP-R1446H and CREBBP loss show different sensitivities to CREBBP/p300 inhibitors.
- Findings have implications for understanding pathogenesis and developing targeted therapies for FL and DLBCL.