ArticleBlood advances2021
Oxidized mitochondrial DNA released after inflammasome activation is a disease biomarker for myelodysplastic syndromes.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Inflammatory Signatures in MDS: The Missing Link Between Genetics, Microenvironment, and Therapy.Cells · 2026Review
- Analysis of the NLRP3 inflammasome components expression in triple-negative breast cancer patients with and without BRCA1 mutations.Scientific reports · 2026Article
- Programmed cell death regulates hematopoietic cell homeostasis under radiation conditions.Stem cell research & therapy · 2025Article
- Novel Perspectives in Hepatic Ischemia-Reperfusion Injury: The cGAS-STING Pathway.Journal of inflammation research · 2025Review
- Inflammation and DNA methylation in Alzheimer's disease: mechanisms of epigenetic remodelling by immune cell oxidants in the ageing brain.Redox report : communications in free radical research · 2024Review
- Implications for metabolic disturbances in myelodysplastic syndromes.Seminars in hematology · 2024Review
- Potential Diagnostic Value of Abnormal Pyroptosis Genes Expression in Myelodysplastic Syndromes (MDS): A Primary Observational Cohort Study.International journal of hematology-oncology and stem cell research · 2024Article
- Unraveling the Role of the NLRP3 Inflammasome in Lymphoma: Implications in Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Toll-Like Receptor 4, 2, and Interleukin 1 Receptor Associated Kinase4: Possible Diagnostic Biomarkers in Myelodysplastic Syndrome Patients.Advanced biomedical research · 2024Article
- Circulating Oxidized mtDNA is Associated Broadly with Cardiovascular Disease in a Longitudinal Cohort Study of Psoriasis.JID innovations : skin science from molecules to population health · 2024Article
- Inhibition of SF3B1 improves the immune microenvironment through pyroptosis and synergizes with αPDL1 in ovarian cancer.Cell death & disease · 2023Article
- The implication of pyroptosis in cancer immunology: Current advances and prospects.Genes & diseases · 2023Review
- Article
- Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity.International journal of molecular sciences · 2023Review
- The Role of NLRP3, a Star of Excellence in Myeloproliferative Neoplasms.International journal of molecular sciences · 2023Review
- Oxidized Mitochondrial DNA Engages TLR9 to Activate the NLRP3 Inflammasome in Myelodysplastic Syndromes.International journal of molecular sciences · 2023Article
- Pyroptosis Markers in Human Primary Specimens: Quantification of Intracellular ASC Specks by Imaging Flow Cytometry and Extracellular Oxidized Mitochondrial by ELISA.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Inflammasomes-New Contributors to Blood Diseases.International journal of molecular sciences · 2022Review
- Acquired and hereditary bone marrow failure: A mitochondrial perspective.Frontiers in oncology · 2022Review
- Next generations of CAR-T cells - new therapeutic opportunities in hematology?Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
Abstract
Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem cell malignancies that can phenotypically resemble other hematologic disorders. Thus, tools that may add to current diagnostic practices could aid in disease discrimination. Constitutive innate immune activation is a pathogenetic driver of ineffective hematopoiesis in MDS through Nod-like receptor protein 3 (NLRP3)-inflammasome-induced pyroptotic cell death. Oxidized mitochondrial DNA (ox-mtDNA) is released upon cytolysis, acts as a danger signal, and triggers inflammasome oligomerization via DNA sensors. By using immortalized bone marrow cells from murine models of common MDS somatic gene mutations and MDS primary samples, we demonstrate that ox-mtDNA is released upon pyroptosis. ox-mtDNA was significantly increased in MDS peripheral blood (PB) plasma compared with the plasma of healthy donors, and it was significantly higher in lower-risk MDS vs higher-risk MDS, consistent with the greater pyroptotic cell fraction in lower-risk patients. Furthermore, ox-mtDNA was significantly higher in MDS PB plasma compared with all other hematologic malignancies studied, with the exception of chronic lymphocytic leukemia (CLL). Receiver operating characteristic/area under the curve (ROC/AUC) analysis demonstrated that ox-mtDNA is a sensitive and specific biomarker for patients with MDS compared with healthy donors (AUC, 0.964), other hematologic malignancies excluding CLL (AUC, 0.893), and reactive conditions (AUC, 0.940). ox-mtDNA positively and significantly correlated with levels of known alarmins S100A9, S100A8, and apoptosis-associated speck-like protein containing caspase recruitment domain (CARD) specks, which provide an index of medullary pyroptosis. Collectively, these data indicate that quantifiable ox-mtDNA released into the extracellular space upon inflammasome activation serves as a biomarker for MDS and the magnitude of pyroptotic cell death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.