V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules
Received 19 October 2006; received in revised form 19 January 2007; accepted 29 January 2007.
Refers to erratum:
Erratum
Experimental Hematology
September 2007 (Vol. 35, Issue 9, Pages 1476.e1-1476.e11) Full Text |
Full-Text PDF (309 KB)
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.
Patients and 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.
Department of Hematology-Oncology, Ospedali Riuniti, Bergamo, Italy
Offprint requests to: Anna Falanga, M.D., Department of Hematology, Ospedali Riuniti di Bergamo, Largo Barozzi 1-24128, Bergamo, Italy