title: High prevalence of arterial thrombosis in JAK2 mutated essential thrombocythaemia: independence of the V617F allele burden.
abstract: Approximately half of the patients with essential thrombocythaemia (ET) harbor the JAK2 V617F mutation. Despite a phenotypic mimicry of JAK2 V617F positive ET and polycythaemia vera (PV), the data on thromboembolic risk and correlation to JAK2 mutation status are ambiguous. On a strictly WHO defined ET cohort we evaluated possible clinical correlations to the JAK2 mutation status including a history of previous thrombosis. We used a highly sensitive quantitative real-time PCR (qPCR) assay for JAK2 V617F detection and allele burden quantification in a single institution study of 55 patients. A significantly increased prevalence of arterial thrombosis was recorded in JAK2 positive ET (p=0.001). There was no association between the mutational load and thrombosis. As compared to their JAK2 V617F negative counterparts, the JAK2 V617F positive patients had PV-like biochemical characteristics such as higher haemoglobin levels (p=0.02), lower platelet counts (p=0.002) and lower plasma EPO levels (p=0.04). The JAK2 V617F mutation per se but not the mutational load in patients with ET is associated with a PV-like phenotype and a higher prevalence of previous arterial thrombosis. This study adds further support to the contention of the JAK2 V617F mutation as a marker of increased risk of thrombosis.
authors.affiliation: Department of Haematology, Odense University Hospital, Denmark. thomas.stauffer.larsen@ouh.regionsyddanmark.dk
authors.forename: Thomas Stauffer
authors.initials: TS
authors.lastname: Larsen
authors.forename: Niels
authors.initials: N
authors.lastname: Pallisgaard
authors.forename: Michael Boe
authors.initials: MB
authors.lastname: Møller
authors.forename: Hans Carl
authors.initials: HC
authors.lastname: Hasselbalch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D011087:Polycythemia Vera; D016133:Polymerase Chain Reaction; D015995:Prevalence; D013920:Thrombocythemia, Essential / Q000150:complications* / Q000235:genetics*; D013927:Thrombosis / Q000209:etiology* / Q000235:genetics
chemical_list: D053614:Janus Kinase 2