Influence of JAK2V617F allele burden on phenotype in essential thrombocythemia

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.