title: The JAK2 V617F mutational status and allele burden may be related with the risk of venous thromboembolic events in patients with Philadelphia-negative myeloproliferative neoplasms.
abstract: BACKGROUND
  Patients with Philadelphia-negative myeloproliferative neoplasms (Ph(-) MPNs) are at increased risk of thromboembolic and hemorrhagic complications. The aim of the study was to determine the relationship between JAK2 V617F mutational status, JAK2 V617F allele burden and the risk of vascular complications occurrence.
  
  
  METHODS
  Analysis was performed in a cohort of 186 patients diagnosed with polycythemia vera (53), essential thrombocythemia (114), primary myelofibrosis (11), and unclassified MPN (8). The risk of vascular complications development was analyzed in 126 JAK2 V617F-positive patients with respect to allele burden assessed with allele-specific 'real-time' quantitative polymerase chain reaction (AS RQ-PCR).
  
  
  RESULTS
  Overall prevalence of any vascular complications was 44.6%. Arterial thrombosis occurred in 20.4%, venous thromboembolism (VTE) in 11.3%, bleeding episodes in 24.7% of patients. Individuals harboring JAK2 V617F mutation, regardless of MPN type, were at higher risk of VTE (OR=5.15, 95%CI: 1.16-22.90, P=0.024), mainly deep vein thrombosis (DVT). JAK2 allele burden higher than 20% identified patients with 7.4-fold increased risk of VTE (95%CI: 1.6-33.7, P=0.004), but not of arterial thrombosis, neither of bleeding complications, and remained the only significant VTE risk factor in multivariate logistic regression. High allele burdens (over 50%) were strikingly associated with proximal DVT cases, but not with distal DVT.
  
  
  CONCLUSIONS
  The group of MPN patients with JAK2 V617F allele burden higher than 20% may benefit the most from vigilant monitoring and appropriate prophylaxis against vascular events. Inclusion of JAK2 V617F mutant allele burden in new risk stratifications seems to be justified and requires controlled prospective trials.
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland. Electronic address: martyna.borowczyk@gmail.com.
authors.forename: Martyna
authors.initials: M
authors.lastname: Borowczyk
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Wojtaszewska
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lewandowski
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Gil
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Lewandowska
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Lehmann-Kopydłowska
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Kroll-Balcerzak
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Balcerzak
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Iwoła
authors.affiliation: Department of Computer Science and Statistics, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Komarnicki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D006470:Hemorrhage / Q000235:genetics*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000097:blood / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D054556:Venous Thromboembolism / Q000097:blood / Q000235:genetics*
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Hemorrhage; JAK 2; Myeloproliferative neoplasms; Quantitative real-time polymerase chain reaction; Thrombosis