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December 8, 2025Blood Cancer Discovery

Human TET2-mutant clonal hematopoiesis expansion is driven by distinct inflammatory signaling responses in stem cells versus myeloid progeny.

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Authors

HEHector Huerga EncaboKHKarl HabelMLMiriam Llorian

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Overview

Research demonstrates clonal hematopoiesis affects systemic inflammation in stem cells and myeloid progeny, suggesting new therapeutic insights.

Key Points

  • To understand how TET2 mutations impact clonal hematopoiesis and the immune response in different cell types.
  • Utilized multi-omic analyses on human cells to assess effects of TET2 mutations
  • Analyzed the impact on hematopoietic stem and progenitor cells (HSPC) versus myeloid progeny
  • Examined transcriptional responses to systemic inflammation
  • TET2-mutant HSPCs showed intrinsic epigenetic silencing of AP-1 transcription factors
  • HSPCs exhibited a blunted response to systemic inflammation
  • Myeloid cells from TET2-mutant HSCs contributed to increased inflammation

Cite This Study

Encabo et al. (2025) studied this question.

synapsesocial.com/papers/693624c34fa91c937236cbcfhttps://doi.org/10.1158/2643-3230.bcd-25-0070
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Also Consider

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

  1. 1Bone marrow environmental alterations underlie proliferative clonal expansion in clonal hematopoiesis2025
  2. 2Single-cell multiomic profiling of gene mutation, chromatin accessibility, and gene expression in TET2-mutant clonal hematopoiesis2025
  3. 3Differential sensitivity to LINE 1-induced damage contributes to the expansion of Tet2-deficient HSCs upon chronic inflammatory stress2025 · 1 citations
  4. 4Clonal hematopoiesis drives T cell dysregulation and immune remodeling revealed by GWAS-based mendelian randomization and single-cell transcriptomics2025
  5. 5Chromodomain helicase DNA binding protein CHD2 interacts with TET2 and regulates lineage defining transcription in hematopoietic stem and progenitor cells2025