ArticleThe Journal of clinical investigation2024
Multiomic profiling reveals metabolic alterations mediating aberrant platelet activity and inflammation in myeloproliferative neoplasms.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Toward standardization and a concerted vision for platelet proteomics research: communication from the SSC of the ISTH.Journal of thrombosis and haemostasis : JTH · 2025Guideline
- miR-146a mimic therapy protects against platelet-mediated thrombosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Tumor-educated platelets in cancer diagnostics and prognostics: A critical appraisal and roadmap for clinical translation.International journal of cancer · 2026Review
- Scalable genotyping in fixed transcriptomes resolves clonal heterogeneity via single-cell sequencing.bioRxiv : the preprint server for biology · 2026Article
- Amino acid balancing and microalgal proteins (Spirulina) improve production performance and milk quality in dairy cows under low-protein diets.NPJ science of food · 2026Article
- Physiological MplW514L expression in hematopoietic stem cell causes an essential thrombocythemia and progressive myelofibrosis.The Journal of clinical investigation · 2026Article
- Platelet mTOR Is a Regulator of Sterile Immunothrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- DARS expression in JAK2V617F-positive myeloproliferative neoplasms: immunohistochemical analysis and clinical associations.Annals of hematology · 2026Article
- Review
- Proteomic profiling of high purity extracellular vesicle subtypes from megakaryoblastic leukemia cells provides insights into myeloproliferative neoplasm biology.Extracellular vesicles and circulating nucleic acids · 2026Article
- A proteogenomic gene signature defines prognostic subgroups highlighting PI3K/AKT/mTOR signaling pathway as a therapeutic vulnerability in myeloid malignancies.Cell communication and signaling : CCS · 2025Article
- Article
- Targeting mitochondrial dysfunction in myeloproliferative neoplasms: current strategies and future directions - a narrative review.Annals of medicine and surgery (2012) · 2025Review
- Posttransfusion recovery, quality, and metabolism of short- and long-term stored platelets during controlled inflammation.Blood advances · 2025Article
- Clinical and Molecular Insights of Arterial and Venous Thrombosis in Myeloproliferative Diseases-Case-Based Narrative Review.Biomedicines · 2025Review
- Metabolomic Profiling Reveals Distinct Signatures in Primary and Secondary Polycythemia.Metabolites · 2025Article
- TNF-α impairs platelet function by inhibiting autophagy and disrupting metabolism via syntaxin 17 downregulation.The Journal of clinical investigation · 2025Article
- Article
- Monocyte Involvement in the Pathogenesis of Myeloproliferative Neoplasms.International journal of molecular sciences · 2025Review
- Proteomic and metabolomic analysis of platelet related samples reveals energy metabolism disorders in hepatocellular carcinoma.Journal of translational medicine · 2025Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Platelets from patients with myeloproliferative neoplasms (MPNs) exhibit a hyperreactive phenotype. Here, we found elevated P-selectin exposure and platelet-leukocyte aggregates indicating activation of platelets from essential thrombocythemia (ET) patients. Single-cell RNA-seq analysis of primary samples revealed significant enrichment of transcripts related to platelet activation, mTOR, and oxidative phosphorylation in ET patient platelets. These observations were validated via proteomic profiling. Platelet metabolomics revealed distinct metabolic phenotypes consisting of elevated ATP generation accompanied by increases in the levels of multiple intermediates of the tricarboxylic acid cycle, but lower α-ketoglutarate (α-KG) in MPN patients. Inhibition of PI3K/AKT/mTOR signaling significantly reduced metabolic responses and hyperreactivity in MPN patient platelets, while α-KG supplementation markedly reduced oxygen consumption and ATP generation. Ex vivo incubation of platelets from both MPN patients and Jak2 V617F-knockin mice with α-KG supplementation significantly reduced platelet activation responses. Oral α-KG supplementation of Jak2 V617F mice decreased splenomegaly and reduced hematocrit, monocyte, and platelet counts. Finally, α-KG treatment significantly decreased proinflammatory cytokine secretion from MPN CD14+ monocytes. Our results reveal a previously unrecognized metabolic disorder in conjunction with aberrant PI3K/AKT/mTOR signaling that contributes to platelet hyperreactivity in MPN patients.
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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 OpenQuestion graph.