V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules.
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.
Falanga
Anna
A
Department of Hematology-Oncology, Ospedali Riuniti, Bergamo, Italy. annafalanga@yahoo.com
Marchetti
Marina
M
Vignoli
Alfonso
A
Balducci
Donatella
D
Russo
Laura
L
Guerini
Vittoria
V
Barbui
Tiziano
T
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
D015815:Cell Adhesion Molecules; D006490:Hemostatics; C507924:JAK2 protein, human; D053614:Janus Kinase 2