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February 28, 2026BloodOpen Access

Differential role of CREBBP missense and truncating mutations in germinal center development and lymphomagenesis

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Authors

CYChuanjiang YuMHMara HollomanAKA. K. Kim

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Overview

Differential mutations in CREBBP affect germinal center response and lymphoma initiation, indicating unique impacts on cancer development.

Key Points

  • This research explores how truncating and missense mutations in the CREBBP gene affect germinal center (GC) development and lymphoma initiation.
  • Utilized a conditional GC-specific knock-in mouse model to study CREBBP-R1446H mutations.
  • Compared effects of complete CREBBP loss with missense mutations on GC response.
  • Analyzed distinct transcriptional programs associated with different CREBBP mutations.
  • Missense mutations cause varying effects on the GC response, unlike complete Crebbp loss.
  • CrebbpRH mutant promotes pre-neoplastic GC expansion and alters immune response to favor memory B-cell differentiation.
  • Lymphoma cells with different CREBBP mutations show varied sensitivity to CREBBP/p300 inhibitors.

Cite This Study

Yu et al. (2026) studied this question.

synapsesocial.com/papers/69a286eb0a974eb0d3c023d0https://doi.org/10.1182/blood.2025031181
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