ArticleThe Lancet. Haematology2018
Assessment of ASC specks as a putative biomarker of pyroptosis in myelodysplastic syndromes: an observational cohort study.
Article in The Lancet. Haematology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pyroptosis in Peripheral Neuropathy: From Molecular Mechanisms to Therapeutic Targeting.CNS neuroscience & therapeutics · 2026Pooled it
- One adaptor, multiple outcomes: decoding TRIFosome heterogeneity.Biochemical Society transactions · 2026Review
- Therapeutic Silencing of Tmprss6 Reduces Iron-Induced Inflammation and Prolongs Survival in MDS Mice.American journal of hematology · 2026Article
- OLT1177 (Dapansutrile) inhibits Gasdermin D-dependent IL-1β Release and Pyroptotic Cell Death in Bone Marrow-derived Macrophages.bioRxiv : the preprint server for biology · 2026Article
- Characterization of Genetic Landscape and Novel Inflammatory Biomarkers in Patients With Adult-Onset Still's Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- FACS-based detection of extracellular ASC specks from NLRP3 inflammasomes in inflammatory diseases.Clinical and experimental immunology · 2025Article
- Immune-dysregulation harnessing in myeloid neoplasms.Cancer medicine · 2024Review
- "Cruising together"-ASC specks and SAA, a perfect match in chronic inflammation.EMBO molecular medicine · 2024Article
- CXCL8 and its cognate receptors CXCR1/CXCR2 in primary myelofibrosis.Haematologica · 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
- Multiomics characterization of pyroptosis in the tumor microenvironment and therapeutic relevance in metastatic melanoma.BMC medicine · 2024Article
- ASC speck serum concentrations, a component of sterile cellular inflammation, are associated with individual cardiopulmonary capacity.Frontiers in physiology · 2024Article
- Toll-Like Receptor 4, 2, and Interleukin 1 Receptor Associated Kinase4: Possible Diagnostic Biomarkers in Myelodysplastic Syndrome Patients.Advanced biomedical research · 2024Article
- NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy.Cell reports. Medicine · 2023Article
- Canonical and non-canonical functions of NLRP3.Journal of advanced research · 2023Review
- Current Therapeutic Landscape in Lower Risk Myelodysplastic Syndromes.Current treatment options in oncology · 2023Review
- Oxidized Mitochondrial DNA Engages TLR9 to Activate the NLRP3 Inflammasome in Myelodysplastic Syndromes.International journal of molecular sciences · 2023Article
- NLRP3 inflammasome in neurodegenerative disease.Translational research : the journal of laboratory and clinical medicine · 2023Review
- 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
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Abstract
backgroundNLRP3 inflammasome-directed pyroptotic cell death drives ineffective haemopoiesis in myelodysplastic syndromes. During inflammasome assembly, the apoptosis-associated speck-like protein containing a CARD (PYCARD, commonly known as ASC) adaptor protein polymerises into large, filamentous clusters termed ASC specks that are released upon cytolysis. Specks are resistant to proteolytic degradation because of their prion-like structure, and therefore might serve as a biomarker for pyroptotic cell death in myelodysplastic syndromes.
methodsThis observational cohort study was done at the H Lee Moffitt Cancer Center (Tampa, FL, USA). Patients with myelodysplastic syndromes, healthy controls, and patients with non-myelodysplastic syndrome haematological cancers or type 2 diabetes were recruited. We used confocal and electron microscopy to visualise, and flow cytometry to quantify, ASC specks in peripheral blood and bone marrow plasma samples. Speck percentages were compared by t test or ANOVA, correlations were assessed by Spearman's rank correlation coefficient, and biomarker efficiency was assessed by receiver operating characteristics and area under the curve (AUC) analysis.
findingsBetween Jan 1, 2005, and Jan 12, 2017, we obtained samples from 177 patients with myelodysplastic syndromes and 29 healthy controls for the discovery cohort, and 113 patients with myelodysplastic syndromes and 31 healthy controls for the validation cohort. We also obtained samples from 22 patients with del(5q) myelodysplastic syndromes, 230 patients with non-myelodysplastic syndrome haematological cancers and 23 patients with type 2 diabetes. After adjustment for glucose concentration, the log
interpretationOur results underscore the pathobiological relevance of ASC specks and suggest that ASC specks are a sensitive and specific candidate plasma biomarker that provides an index of medullary pyroptotic cell death and ineffective haemopoiesis in patients with myelodysplastic syndromes.
fundingT32 Training Grant (NIH/NCI 5T32 CA115308-08), Edward P Evans Foundation, The Taub Foundation Grants Program, the Flow Cytometry, Analytic Microscopy, and Tissue Core Facilities at the H Lee Moffitt Cancer Center and Research Institute, a National Cancer Institute-designated Comprehensive Cancer Center (P30-CA076292).
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