ArticleCell death & disease2021
Cytoplasmic DNA accumulation preferentially triggers cell death of myeloid leukemia cells by interacting with intracellular DNA sensing pathway.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 32 citations in OpenAlex.
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- Enlarged PML-nuclear bodies trigger conflicting cell cycle signal-mediated cytotoxicity in leukemia cells.Cell death & disease · 2025Article
- Novel Personalized Cancer Vaccine Using Tumor Extracellular Vesicles with Attenuated Tumorigenicity and Enhanced Immunogenicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Small molecule innate immune modulators in cancer therapy.Frontiers in immunology · 2024Review
- The miRNA Content of Bone Marrow-Derived Extracellular Vesicles Contributes to Protein Pathway Alterations Involved in Ionising Radiation-Induced Bystander Responses.International journal of molecular sciences · 2023Article
- Single-cell transcriptome analysis profiles the expression features of TMEM173 in BM cells of high-risk B-cell acute lymphoblastic leukemia.BMC cancer · 2023Article
- Crosstalk between cytotoxic CD8+ T cells and stressed cardiomyocytes triggers development of interstitial cardiac fibrosis in hypertensive mouse hearts.Frontiers in immunology · 2022Article
- How the Innate Immune DNA Sensing cGAS-STING Pathway Is Involved in Autophagy.International journal of molecular sciences · 2021Review
- KDM6A mutations promote acute cytoplasmic DNA release, DNA damage response and mitosis defects.BMC molecular and cell biology · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence indicates the presence of cytoplasmic DNAs in various types of malignant cells, and its involvement in anti-cancer drug- or radiotherapy-mediated DNA damage response and replication stress. However, the pathophysiological roles of cytoplasmic DNAs in leukemias remain largely unknown. We observed that during hematopoietic stem cell transplantation (HSCT) in mouse myeloid leukemia models, double-stranded (ds)DNAs were constitutively secreted in the form of extracellular vesicles (EVs) from myeloid leukemia cells and were transferred to the donor cells to dampen their hematopoietic capabilities. Subsequent analysis of cytoplasmic DNA dynamics in leukemia cells revealed that autophagy regulated cytoplasmic dsDNA accumulation and subsequent redistribution into EVs. Moreover, accumulated cytoplasmic dsDNAs activated STING pathway, thereby reducing leukemia cell viability through reactive oxygen species (ROS) generation. Pharmaceutical inhibition of autophagosome formation induced cytoplasmic DNA accumulation, eventually triggering cytoplasmic DNA sensing pathways to exert cytotoxicity, preferentially in leukemia cells. Thus, manipulation of cytoplasmic dsDNA dynamics can be a novel and potent therapeutic strategy for myeloid leukemias.
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