V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules

Exp Hematol. 2007 May;35(5):702-11. doi: 10.1016/j.exphem.2007.01.053.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Substitution
  • Blood Platelets / metabolism*
  • Cell Adhesion Molecules / blood
  • Cell Adhesion Molecules / metabolism*
  • Female
  • Granulocytes / metabolism*
  • Hemostatics / blood
  • Hemostatics / metabolism*
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Thrombocythemia, Essential / diagnosis
  • Thrombocythemia, Essential / genetics*
  • Thrombocythemia, Essential / metabolism

Substances

  • Cell Adhesion Molecules
  • Hemostatics
  • JAK2 protein, human
  • Janus Kinase 2