ArticleThe Journal of clinical investigation2018
JAK2-V617F promotes venous thrombosis through β1/β2 integrin activation.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 134 citations in OpenAlex.
- Trial
- Extensive Cerebral Venous Sinus Thrombosis With Obstructive Hydrocephalus in a Young Female With Underlying Essential Thrombocythemia: A Case Report.Clinical case reports · 2026Article
- Clinical management of clonal hematopoiesis.Cancer · 2026Review
- Clonal hematopoiesis and thrombosis risk-what are research and clinical gaps?Research and practice in thrombosis and haemostasis · 2026Review
- Clonal Hematopoiesis of Indeterminate Potential (CHIP): A Model of Mutation-Driven Thromboinflammation.Cancers · 2026Review
- Megakaryocytic Emperipolesis in Acute Myeloid Leukemia with Trisomy 8Turkish journal of haematology : official journal of Turkish Society of Haematology · 2026Article
- Clonal Hematopoiesis of Indeterminate Potential and Cardiometabolic Disease: Challenges, Controversies and Future Perspectives.International journal of molecular sciences · 2025Review
- Molecular Mechanism of Notch Signaling and Macrophages in Deep Vein Thrombosis: A Comprehensive Review.Cell biochemistry and biophysics · 2025Review
- Activation of integrin signaling up-regulates pro-inflammatory cytokines in JAK2-V617F positive hematopoietic cells.Cell communication and signaling : CCS · 2025Article
- Review
- Clonal Hematopoiesis and Thrombosis.American journal of hematology · 2025Review
- Review
- Molecular predictors of venous and arterial thrombotic events in patients with myelofibrosis.Annals of hematology · 2025Article
- Malignant JAK-signaling: at the interface of inflammation and malignant transformation.Leukemia · 2025Review
- Proinflammatory and prothrombotic conditions in JAK2V617F-positive MPN: a case of Lemierre's syndrome in essential thrombocythemia.Annals of hematology · 2025Article
- [A case of cirrhosis combined with myeloproliferative neoplasms].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Article
- Venous thrombosis and obesity: from clinical needs to therapeutic challenges.Internal and emergency medicine · 2025Review
- Interferon-α Inhibits NET Formation in Neutrophils Derived from Patients with Myeloproliferative Neoplasms in a Neutrophil Sub-Population-Specific Manner.International journal of molecular sciences · 2024Article
- Cardiovascular Risk in Philadelphia-Negative Myeloproliferative Neoplasms: Mechanisms and Implications-A Narrative Review.Current issues in molecular biology · 2024Review
- Exacerbation of thromboinflammation by JAK2V617F mutation worsens the prognosis of cerebral venous sinus thrombosis.Blood advances · 2024Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
JAK2-V617F-positive chronic myeloproliferative neoplasia (CMN) commonly displays dysfunction of integrins and adhesion molecules expressed on platelets, erythrocytes, and leukocytes. However, the mechanism by which the 2 major leukocyte integrin chains, β1 and β2, may contribute to CMN pathophysiology remained unclear. β1 (α4β1; VLA-4) and β2 (αLβ2; LFA-1) integrins are essential regulators for attachment of leukocytes to endothelial cells. We here showed enhanced adhesion of granulocytes from mice with JAK2-V617F knockin (JAK2+/VF mice) to vascular cell adhesion molecule 1- (VCAM1-) and intercellular adhesion molecule 1-coated (ICAM1-coated) surfaces. Soluble VCAM1 and ICAM1 ligand binding assays revealed increased affinity of β1 and β2 integrins for their respective ligands. For β1 integrins, this correlated with a structural change from the low- to the high-affinity conformation induced by JAK2-V617F. JAK2-V617F triggered constitutive activation of the integrin inside-out signaling molecule Rap1, resulting in translocation toward the cell membrane. Employing a venous thrombosis model, we demonstrated that neutralizing anti-VLA-4 and anti-β2 integrin antibodies suppress pathologic thrombosis as observed in JAK2+/VF mice. In addition, aberrant homing of JAK2+/VF leukocytes to the spleen was inhibited by neutralizing anti-β2 antibodies and by pharmacologic inhibition of Rap1. Thus, our findings identified cross-talk between JAK2-V617F and integrin activation promoting pathologic thrombosis and abnormal trafficking of leukocytes to the spleen.
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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.