Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
December 8, 2025BloodOpen Access

The bromodomain and extra-terminal domain protein BRD4 promotes both self renewal and inflammation in TET2 mutated clonal hematopoiesis

View Full Paper
Ask AI
Bookmark
Share

Authors

AMAlexander MarrMHMadeline HalpinBGBritten Gordon

Discussion

Loading...

Member takes

Overview

Study demonstrates BRD4 regulates inflammatory signaling and cytokine production in clonal hematopoiesis, suggesting potential therapeutic targets.

Key Points

  • This research aims to investigate the role of BRD4 in clonal hematopoiesis and its impact on inflammation and myeloid neoplasms.
  • Examined primary blood mononuclear cells (PBMCs) from healthy donors and patients with TET2 mutations.
  • Cultured PBMCs with LPS and PLX51107 to assess cytokine production and signaling pathways.
  • Created a conditional knockout mouse model to study Brd4's effects on Tet2-mediated clonal hematopoiesis.
  • LPS induced heightened cytokine production in CCUS PBMCs compared to healthy donors.
  • Brd4 inhibition reduced cytokine release and inflammatory signaling in both human and mouse models.
  • Competitive repopulation studies showed Brd4 Tet2 DKO cells had no advantage compared to Tet2 KO, indicating crucial roles in hematopoietic stem cell function.

Cite This Study

Marr et al. (2025) studied this question.

synapsesocial.com/papers/693624dd4fa91c937236d241https://doi.org/10.1182/blood-2025-1398
View Full Paper
Ask AI
Bookmark
Share

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Chromodomain helicase DNA binding protein CHD2 interacts with TET2 and regulates lineage defining transcription in hematopoietic stem and progenitor cells2025
  2. 2Impact of innate immune memory on MDS progression by TET2-driven inflammation2025
  3. 3Single-cell multiomic profiling of gene mutation, chromatin accessibility, and gene expression in TET2-mutant clonal hematopoiesis2025
  4. 4Human TET2-mutant clonal hematopoiesis expansion is driven by distinct inflammatory signaling responses in stem cells versus myeloid progeny.2025 · 8 citations
  5. 5TET2 mutations drive cell-autonomous type I interferon production and selective advantage through TRIM4 silencing2025