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December 8, 2025BloodOpen Access

The somatic DDX41 hot spot mutation (p.R525H) causes skewed differentiation into plasmacytoid dendritic cells in human iPSC and leukemia models

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Authors

JKJun‐ichiro KidaESEmily StepanchickTCTimothy M. Chlon

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Overview

Analysis reveals that the DDX41 p.R525H mutation impairs proliferation in hematopoietic progenitors, suggesting a role in denderitic cell differentiation.

Key Points

  • DDX41 p.R525H mutation reduces proliferation of hematopoietic stem and progenitor cells while promoting differentiation into plasmacytoid dendritic cells.
  • Cells with p.R525H mutation formed fewer myeloid and erythroid colonies after DOX withdrawal, indicating impaired function.
  • Assessment used single-cell analysis and flow cytometry to explore the effects of the mutation on dendritic cells in induced pluripotent stem cell models.
  • Dysregulated dendritic cells may contribute to the pathogenesis of myeloid malignancies associated with DDX41 mutations.

Cite This Study

Kida et al. (2025) studied this question.

synapsesocial.com/papers/69362f4e4fa91c937236d8c0https://doi.org/10.1182/blood-2025-678
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