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Influence of JAK2^V617F allele burden on phenotype in essential thrombocythemia

Department of Hematology, University of Florence, Florence, Italy; and the MPD-RC, Mount Sinai Hospital, New York, USA

Correspondence: Alessandro M. Vannucchi, Department of Hematology, University of Florence, 50134, Florence, Italy. E-mail: amvannucchi{at}unifi.it

Background: Fifty to sixty percent of patients with essential thrombocythemia harbor the JAK2^V617F mutation. The impact of this mutation on clinical phenotype is still debated. The aim of this study was to evaluate possible correlations between JAK2^V617F mutant allele burden and both clinical presentation and hematologic abnormalities in essential thrombocythemia patients.

Design and Methods: In this single-center retrospective study, JAK2^V617F allele load was measured by sensitive quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in the granulocytes of 260 patients diagnosed as having essential thrombocythemia according to WHO criteria.

Results: Median V617F allele burden in patients with the mutation (n=165, 63.4%) was 24%, ranging from 1% to 87%; an allele burden greater than 51% was found in 5% of the patients. Older patients presented progressively higher percentages of the V617F allele. Signs of stimulated erythropoiesis and myelopoiesis, as well as higher PRV-1 levels, were found in patients with the mutation, but no linear correlation with load of mutant allele could be ascertained; on the other hand, the frequency of patients with erythropoietin-independent erythroid colonies progressively increased depending on mutant allele load. Splenomegaly and microvessel symptoms were significantly more represented among patients with greater than 50% and 25% JAK2^V617F allele burden, respectively. Increasing mutant allele load correlated with higher frequency of arterial thrombosis at diagnosis, as confirmed also in multivariate analysis; the relative risk was 3.0 (95% CI 1.3–6.8; p=0.01) in patients having a greater than 25% mutant allele burden.

Conclusions: The JAK2^V617F mutant allele burden contributes to determining the clinical phenotype in patients with essential thrombocythemia.

Key words: JAK2^V617F, allele burden, essential thrombocythemia, phenotype.

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