JAK2^V617F Point Mutation In Patients With Polycythemia Vera

Objective:Polycythemia vera(PV),one of the chronic myeloproliferative disorders,is a clonal haematopoietic stem cell malignancy.The clinical course of patients with PV is characterized by the presence of polycythemia diversely associated with thrombocytosis,leukocytosis and splenomegaly,and an increased rate of arterial and venouse thrombosis.Less frequently,the disease might develop myelofibrosis or transforms to acute myeloid leukemia.In polycythemia vera,the mechanisms leading to erythropoietin hypersensitivity and in vitro production of erythroid colonies in the absence of cytokines(endogenous erythroid colonies,EEC) are still unknown.Recently,a somatic point mutation of the Janus kinase 2(JAK2)gene was identified in majority of patients with PV.This point mutation is a G to T transversion,resulting in a nonsynonymous amino acid substitution at position 617(valine to phenylalanine)located in the JH2 pseudo-kinase,leading to increased kinase activity.JAK2^V617Finduces erythropoietin hypersensitivity and erythrocytosis,results in PV.The aim of this study was to investigate the incidence and specificity of JAK2^V617Fmutation in patients with PV,to analyze the correlations between JAK2^V617Fmutational status and clinical,laboratory features,so that we can provide evidencese for the diagnosis,prognosis and management of patients with PV.Methods:By AS-PCR,the expression of JAK2^V617Fof 26 patients with a diagnosed PV,10 patients with secondary erythrocytosis,5 patients with Ph⁺ CML and 5 healthy controls was assayed.And the results were confirmed by sequence analysis.PCR-RFLP was performed to identify the mutation status of JAK2^V617FA statistical analysis between JAK2^V617Fheterozygotes and homozygotes was performed associations with clinical and laboratory characteristic.Results:The JAK2^V617Fmutant allele was detected in 24 of the 26 patients (92.3%).10 patients with secondary erythrocytosis,5 patients with Ph⁺ CML and 5 healthy controls had the wild-type JAK2.Seven of patients with JAK2^V617Fmutant allele were homozygotes,17 patients were heterozygotes.A comparison between the homozygote patients and the heterozygote patients associations with clinical and laboratory revealed significantly higher hemoglobin level at the time of diagnosis in the former group(224.29±6.24 g/L vs.210.29±9.12g/L,p= 0.001).Similarly,a significantly higher LDH level were finded in patients with homozygous JAK2^V617F,compared with those with the heterozygous mutation.However,a statistical comparison between JAK2^V617Fheterozygotes and homozygotes did not reveal any significant associations with regard to age,gender,survival time,leukocyte or platelet count at the time of diagnosis,or the incidences of splenomegaly or hepatomegaly, pruritus,thrombosis and fibrotic transformation.Conclusions:1.JAK2^V617Fmutation was highly expressed in PV.2.JAK2^V617Fmutation maybe becomes the molecular diagnostic criteria of PV.3.The hemoglobin level and LDH level at the time of diagnosis were significantly higher in patients with homozygous JAK2^V617F,compared with those with the heterozygous mutation.