title: V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules.
abstract: OBJECTIVE
  This article evaluates patients with essential thrombocythemia (ET) to determine whether the V617F mutation in the JAK2 gene affects platelet hemostatic and adhesive molecules, platelet-polymorphonuclear leukocyte (PMN) interactions, and PMN-activation characteristics, as well as plasma hypercoagulation markers.
  
  
  METHODS
  Thirty-seven ET patients with V617F JAK2 mutation and 38 wild-type, and 50 healthy controls were studied.
  
  
  RESULTS
  Platelets from overall ET patients, compared to controls, expressed significantly higher membrane tissue factor (TF) and P-selectin (p < 0.01) and lower CD41 and CD42b (p < 0.01). TF appeared significantly higher in the V617F JAK2 carriers compared to wild-type, and total platelet TF antigen levels confirmed the same result. The presence of circulating platelet/PMN aggregates was significantly greater in the JAK2-mutation carriers than in the wild-type and controls (p < 0.05). PMN surface activation and inflammatory markers (i.e., CD14, TF, CD11b, and leukocyte alkaline phosphatase [LAP]) were all significantly higher in ET versus control subjects, with CD14 and LAP being the highest in the JAK2 mutation carriers. Finally, a significant increase in plasma hypercoagulation markers was found in ET patients, and the only difference for the V617F JAK2 carriers was higher plasma thrombomodulin levels (p < 0.01). Differences in white blood cell and PMN count, platelet TF, PMN CD14, and LAP, and plasma thrombomodulin remained significant after multivariate analysis.
  
  
  CONCLUSIONS
  These results show that a correlation exists between the presence of V617F JAK2 mutation and selected hemostatic activation variables.
authors.affiliation: Department of Hematology-Oncology, Ospedali Riuniti, Bergamo, Italy. annafalanga@yahoo.com
authors.forename: Anna
authors.initials: A
authors.lastname: Falanga
authors.forename: Marina
authors.initials: M
authors.lastname: Marchetti
authors.forename: Alfonso
authors.initials: A
authors.lastname: Vignoli
authors.forename: Donatella
authors.initials: D
authors.lastname: Balducci
authors.forename: Laura
authors.initials: L
authors.lastname: Russo
authors.forename: Vittoria
authors.initials: V
authors.lastname: Guerini
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001792:Blood Platelets / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000097:blood / Q000378:metabolism*; D005260:Female; D006098:Granulocytes / Q000378:metabolism*; D006490:Hemostatics / Q000097:blood / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D006490:Hemostatics; C507924:JAK2 protein, human; D053614:Janus Kinase 2