ArticleJournal of thrombosis and haemostasis : JTH2011
Mechanism of platelet factor 4 (PF4) deficiency with RUNX1 haplodeficiency: RUNX1 is a transcriptional regulator of PF4.
Article in Journal of thrombosis and haemostasis : JTH, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Gut Microbiota Regulates Systemic Inflammatory Response and Compensatory Anti-Inflammatory Response Syndromes by Targeting PF4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Platelet factor 4 in cognitive, immune and hematopoietic aging: emerging evidence and translational challenges.Frontiers in immunology · 2026Review
- Hereditary Hematopoietic Malignancies: Considerations for Optimizing Diagnosis and Management.Current oncology reports · 2025Review
- RUNX1 isoforms regulate RUNX1 and target genes differentially in platelets-megakaryocytes: association with clinical cardiovascular events.Journal of thrombosis and haemostasis : JTH · 2024Article
- RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events.bioRxiv : the preprint server for biology · 2024Article
- Altered platelet-megakaryocyte endocytosis and trafficking of albumin and fibrinogen in RUNX1 haplodeficiency.Blood advances · 2024Article
- Dynamin-2 deficiency causes age- and sex-dependent neutropenia and myelodysplasia in mice.Blood advances · 2023Article
- Expansion of Human Megakaryocyte-Lineage Progeny via Aryl Hydrocarbon Receptor Antagonism with CH223191.Stem cell reviews and reports · 2022Article
- Defective RAB31-mediated megakaryocytic early endosomal trafficking of VWF, EGFR, and M6PR in RUNX1 deficiency.Blood advances · 2022Article
- Adult-repopulating lymphoid potential of yolk sac blood vessels is not confined to arterial endothelial cells.Science China. Life sciences · 2021Article
- Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications.International journal of molecular sciences · 2021Review
- Reduced CXCL4/PF4 expression as a driver of increased human hematopoietic stem and progenitor cell proliferation in polycythemia vera.Blood cancer journal · 2021Article
- Article
- Platelet proteome reveals specific proteins associated with platelet activation and the hypercoagulable state in β-thalassmia/HbE patients.Scientific reports · 2019Article
- Defective RAB1B-related megakaryocytic ER-to-Golgi transport in RUNX1 haplodeficiency: impact on von Willebrand factor.Blood advances · 2018Article
- HumanBlood · 2018Article
- Characterization of CADD522, a small molecule that inhibits RUNX2-DNA binding and exhibits antitumor activity.Oncotarget · 2017Article
- Transcription Factor RUNX1 Regulates PlateletCirculation · 2017Article
- Defective acid hydrolase secretion in RUNX1 haplodeficiency: Evidence for a global platelet secretory defect.Haemophilia : the official journal of the World Federation of Hemophilia · 2017Article
- Hematopoietic transcription factor mutations: important players in inherited platelet defects.Blood · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPlatelet factor 4 (PF4) is an abundant protein stored in platelet α-granules. Several patients have been described with platelet PF4 deficiency, including the gray platelet syndrome, characterized by a deficiency of α-granule proteins. Defective granule formation and protein targeting are considered to be the predominant mechanisms. We have reported on a patient with thrombocytopenia and impaired platelet aggregation, secretion, and protein phosphorylation, associated with a mutation in the transcription factor RUNX1. Platelet expression profiling showed decreased transcript expression of PF4 and its non-allelic variant PF4V1.
objectivesTo understand the mechanism leading to PF4 deficiency associated with RUNX1 haplodeficiency, we addressed the hypothesis that PF4 is a transcriptional target of RUNX1. METHODS/
resultsChromatin immunoprecipitation and gel-shift assays with phorbol 12-myristate 13-acetate-treated human erythroleukemia (HEL) cells revealed RUNX1 binding to RUNX1 consensus sites at -1774/-1769 and -157/-152 on the PF4 promoter. In luciferase reporter studies in HEL cells, mutation of each site markedly reduced activity. PF4 promoter activity and PF4 protein level were decreased by small interfering RNA RUNX1 knockdown and increased by RUNX1 overexpression.
conclusionsOur results provide the first evidence that PF4 is regulated by RUNX1 and that impaired transcriptional regulation leads to the PF4 deficiency associated with RUNX1 haplodeficiency. Because our patient had decreased platelet albumin and IgG (not synthesized by megakaryocytes) levels, we postulate additional defects in RUNX1-regulated genes involved in vesicular trafficking. These studies advance our understanding of the mechanisms in α-granule deficiency.
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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 OpenQuestion graph.