The most common causes of morbidity and mortality in myeloproliferative neoplasms (MPN) are thrombotic and hemorrhagic complications. The JAK2V617F mutation, commonly found in MPN, correlates with several clinical and laboratory characteristics even if the relevance of JAK2V617F allele burden in the natural history of these diseases is unclear. In this study we searched, a relation between thrombotic and hemorrhagic complications and JAK2V617F allele burden level in MPN patients. We evaluated 253 consecutive MPN [121 essential thrombocythemia (ET), 124 polycythemia vera (PV), and 8 primary myelofibrosis (PMF)] patients in whom the JAK2V617F allele burden was available, all studied and followed (median 8.8 years) in our department. Patients were stratified accordingly to their JAK2V617F allele burden, into four quartiles (1st <25%, 2nd 26-50%, 3rd 51-75%, and 4th >75%). Significantly higher incidence of thromboses (p = 0.001) and hemorrhages (p < 0.001) during follow-up has been observed in higher quartiles when compared to lower ones. Thrombosis- and hemorrhage-free survivals were poorer in patients belonging to the highest quartile. Our data suggest that MPN patients with JAK2V617F allele burden higher than 75% have to be considered as high risk patients, being prone to develop thrombo-hemorrhagic complications during the disease course.
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http://dx.doi.org/10.1007/s00277-017-3040-8 | DOI Listing |
Hamostaseologie
December 2024
Klinik für Innere Medizin II, Abteilung Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany.
Background: The risk of thrombosis and bleeding in myelofibrosis (MF) has been historically underappreciated. We sought to investigate potential molecular and clinical risk factors for venous (VTE) and arterial (ATE) thrombotic events as well as bleeding episodes.
Methods: Data from 246 consecutive MF patients were analyzed.
Thromb Res
January 2025
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Neurology, Zealand University Hospital, Roskilde, Denmark.
Background: The JAK2V617F mutation is a driver of Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) and is also implicated in cardiovascular diseases. Thrombosis in MPN involves JAK2V617F-associated platelet activation and endothelial dysfunction, all potentially influenced by chronic inflammation. Whether the mutation affects thromboinflammatory markers similarly in non-MPN patients remains unclear.
View Article and Find Full Text PDFCancer
January 2025
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was approved by the US Food and Drug Administration in 2014 for treatment of patients with polycythemia vera (PV) who have an inadequate response to or intolerance of hydroxyurea (HU). PV is a chronic myeloproliferative neoplasm defined by primary absolute erythrocytosis, bone marrow hypercellularity, and JAK mutations such as JAK2V617F. Patients with PV experience burdensome symptoms and are at risk of thromboembolic events, in particular those with resistance to or intolerance of initial treatments such as HU.
View Article and Find Full Text PDFHematology
December 2024
Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Objectives: Hemorrhagic events are a rare but potentially fatal complication in patients with polycythemia vera (PV).
Methods: We analyzed the characteristics of hemorrhagic events in 267 patients with PV.
Results: A median follow-up of 4.
J Clin Invest
November 2024
Division of Molecular Medicine, Department of Medicine, and.
Clonal hematopoiesis (CH) increases inflammasome-linked atherosclerosis, but the mechanisms by which CH mutant cells transmit inflammatory signals to nonmutant cells are largely unknown. To address this question, we transplanted 1.5% Jak2V617F (Jak2VF) bone marrow (BM) cells with 98.
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