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December 8, 2025Blood

Dnmt3a-mutant hematopoietic stem cells generate alloreactive T cells with graft vs host disease and graft vs leukemia effects

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Authors

MEMark EngelkenCHCyrielle HolukaQZQiong Zhang

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Overview

Conditional knockin Dnmt3a mutations enhance GVHD and GVL activity in T cells of allogeneic transplant models, suggesting significant implications for transplanted patients.

Key Points

  • This research aims to determine the effects of DNMT3A mutations in hematopoietic stem cells on T cell function and related outcomes.
  • Utilized a conditional knockin murine model of Dnmt3aR878H/+ mutations.
  • Conducted immunophenotyping and flow cytometry analyses of T cell populations.
  • Used adoptive transfer to assess alloreactivity of naïve CD4+ T cells.
  • Evaluated GVL activity using an aggressive AML cell line in vivo.
  • Dnmt3aR878H/+ mice develop severe ulcerative dermatitis and exhibit increased CD4+ T cell populations.
  • Naïve CD4+ T cells from mutant mice show enhanced alloreactive responses and earlier GVHD onset.
  • In vitro, mutant T cells kill AML cells more effectively than wild-type cells, correlating with improved survival in vivo.

Cite This Study

Engelken et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dcf5https://doi.org/10.1182/blood-2025-7618
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  3. 3Clonal Hematopoiesis-Associated Gene Mutations Affect Acute Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation in AML Patients2024 · 2 citations
  4. 4Mesenchymal Stromal Cell Senescence Induced by Dnmt3a-Mutant Hematopoietic Cells is a Targetable Mechanism Driving Clonal Hematopoiesis and Initiation of Hematologic Malignancy2024 · 13 citations
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