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JAK2V617F mutation in platelets from essential thrombocythemia patients: correlation with clinical features and analysis of STAT5 phosphorylation status

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Heller PG, Lev PR, Salim JP, Kornblihtt LI, Goette NP, Chazarreta CD, Glembotsky AC, Vassallu PS, Marta RF, Molinas FC. JAK2V617F mutation in platelets from essential thrombocythemia patients: correlation with clinical features and analysis of STAT5 phosphorylation status. Abstract:  Objective: 

JAK2V617F mutation rate in granulocytes from essential thrombocythemia (ET) patients ranges from 12% to 57%. Our aim was to evaluate the frequency of this mutation in the megakaryocyte/platelet lineage, and to analyze its clinical associations in ET. In addition, we determined whether this mutation leads to constitutive phosphorylation of STAT5 in platelets. Materials and Methods: 

Consecutive patients with ET were included and clinical features were retrospectively reviewed. Mutation detection was performed by allele specific RT-PCR (AS-RT-PCR) and Restriction fragment length polymorphism (RFLP) analysis of platelet RNA. Constitutive phosphorylation of STAT5 in platelets was studied by Western blot. Results: 

Fifty patients were included, 24 (48%) were JAK2V617F-positive by both AS-RT-PCR and RFLP. Patients with the mutation were older, had significantly higher hemoglobin levels, and lower platelet counts. Besides, higher frequency of thrombotic events was found in JAK2V617F-positive patients younger than 60, 53% vs. 4%, P = 0.0008. In addition, constitutive STAT5 phosphorylation was not detected in platelets from 12 patients. Conclusions: 

The frequency of the JAK2V617F mutation in platelets was similar to that reported in granulocytes in the literature, suggesting this mutation does not occur as an isolated event in the megakaryocyte lineage. If confirmed in a larger study, the observed higher frequency of thrombosis in patients younger than 60 might be a useful predictive marker for thrombosis in this subset of patients. Even though this mutation has been predicted to constitutively activate the JAK2 kinase, spontaneous phosphorylation of STAT5 does not seem to be a frequent finding in platelets from ET patients.
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Keywords: JAK2V617F; STAT5; essential thrombocythemia; platelets; thrombosis

Document Type: Research Article

Publication date: September 1, 2006

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