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Updated: Nov 11, 2025

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
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Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

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Cytoplasmic DNA accumulation preferentially triggers cell death of myeloid leukemia cells by interacting with

Tomohisa Baba1, Takeshi Yoshida2,3, Yamato Tanabe4

  • 1Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. sergenti@staff.kanazawa-u.ac.jp.

Cell Death & Disease
|March 27, 2021
PubMed

Insights

Cytoplasmic double-stranded (ds)DNAs secreted by leukemia cells in extracellular vesicles (EVs) impair donor cell function. Targeting dsDNA dynamics and autophagy offers a novel therapeutic strategy for myeloid leukemias.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Cytoplasmic DNAs are implicated in cancer drug/radiotherapy responses.
  • The role of cytoplasmic DNAs in leukemias is not well understood.

Purpose of the Study:

  • To investigate the pathophysiological roles of cytoplasmic DNAs in myeloid leukemias.
  • To explore therapeutic strategies targeting cytoplasmic DNA dynamics.

Main Methods:

  • Hematopoietic stem cell transplantation (HSCT) in mouse myeloid leukemia models.
  • Analysis of cytoplasmic DNA dynamics, autophagy, and extracellular vesicle (EV) secretion.
  • STING pathway activation and reactive oxygen species (ROS) generation assays.
  • Pharmaceutical inhibition of autophagosome formation.

Main Results:

  • Leukemia cells constitutively secreted dsDNAs via EVs, impairing donor cell hematopoiesis.
  • Autophagy regulated cytoplasmic dsDNA accumulation and EV loading.
  • Accumulated cytoplasmic dsDNAs activated the STING pathway, reducing leukemia cell viability via ROS.
  • Inhibiting autophagosome formation increased cytoplasmic dsDNA, triggering cytotoxicity in leukemia cells.

Conclusions:

  • Cytoplasmic dsDNA dynamics are crucial in myeloid leukemia pathogenesis.
  • Targeting autophagy and cytoplasmic dsDNA sensing pathways presents a novel therapeutic strategy for myeloid leukemias.

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