Study On The Relationship Between JAK2V617F Gene Mutation And Clinical Characteristics Of BCR/ABL Negative Myeloproliferative Neoplasms

Objective: This research is undertaken to detect the mutation in theJAK2V617gene qualitatively in patients with myeloproliferative neoplasms(MPN) while the BCR/ABL gene is negative and to discuss the correlationbetween the JAK2V617gene mutation and the diagnosis, clinicalcharacteristics, vascular complications of patients with MPN and furthermoreto analysis the risk factors of vascular complications for JAK2V617F genemutation positive patients.Methods： This study retrospectively analyzes136BCR/ABL negativepatients with MPN diagnosis in our hospital between2009Jan. and2012Jan.which include64patients with PV,57patients with ET,15patients with PMF.JAK2V617F gene mutations are detected with allele specific polymerase chainreaction (AS-PCR) method. We evaluate the diagnostic value of the JAK2V-617F gene mutations and the relations between the clinical character-istics,vascular complications and furthermore analysis the risk factors of vascularcomplications for JAK2V617F gene mutation positive patients. The data areanalyzed by the SPSS17.0. Continuous variables were given as mean±1SD,the student t is used in determining differences between mean values betweengroups. Categorical variables were reported as percentages and were analyzedby either Chi-square or Fisher’s exact test, as appropriate. P <0.05wasconsidered statistically significant.Results:1. JAK2V617F gene mutation were detected in all136BCR/ABL negativepatients with MPN,117(86.0%,117/136) turned out to be positive, which include56(87.5%,56/64) PV patients,49(86.0%,49/57) ET patients,12(80.0%,12/15) PMF patients.2. In all BCR/ABL negative patients with MPN, compared with thosewhose gene mutation were negative, JAK2V617gene mutation positivepatients has higher WBC count, especially in PV patients (P＝0.002), followingby ET(P＝0.021) and PMF patients(P＝0.043). Besides, among JAK2V617gene mutation positive patients, ET patients have higher Hb level than thenegative patients (P＝0.033), while the Hb levels in PV and PMF patients haveno statistical differences. Among JAK2V617gene mutation positive patients,the PV group and ET group have a higher platelet level than the JAK2V617negative patients (P＜0.05). The PMF patients have no statistical difference.Other factors such as gender, age, hepatomegaly, splenomegaly, diabetes,hyperlipidemia are compared and results showed that all P values are over0.05.3. The136patients’ cohort includes117JAK2V617gene mutationpositive patients and19JAK2V617negative patients. The baseline factors suchas gender, age, hypertension, diabetes, hyperlipidemia, smoking and drugapplication are compared and results showed that all P values are over0.05,which means no statistical difference. Two group of each factor in baseline arecomparable. JAK2V617gene mutation positive patients are more likely todevelop vascular complications (P=0.054), among which the cardiovasculardiseases are the most common(74.7%，P=0.023), following by deep veinthrombus(18.6%，P=0.043). Among these, ET group are more likely to developdeep veins thrombus while the PV group patients are susceptible tocardiovascular disease.(29/56,51.8%) Multivariate analysis suggests thatamong the JAK2V617F gene mutation positive patients, the risk factors ofvascular complications include advanced age(＞60,P=0.038)，hyperlipidemia(P=0.002) and WBC(P=0.063).On the contrary, sex(P=0.007), smoking(P=0.951) and have no statistical significance. ROC curve indicates the WBC cut point for vascular complications is14.72×109/L.Patients whose WBC abovethis value are vulnerable to develop vascular complications.Conclusions:1. JAK2V617F gene mutation plays an important role in the diagnose ofPV, ET and PMF.2. In all BCR/ABL negative patients with MPN, compared with thosewhose gene mutation were negative, JAK2V617gene mutation positivepatients has some different clinical characteristics. In PV, ET and PMF patients,JAK2V617F positive patients have a high level of WBC counts. The genemutation positive ET patients have a high level of Hb. The gene mutationpositive PV and ET patients have a high level of PLT count. Other factors suchas gender, age, hepatomegaly, splenomegaly，diabetes, hyperlipidemia arecompared and results showed that all P values are over0.05.3. JAK2V617gene is related with the vascular complications. Among thevarious complications, ET patients are more likely to develop deep veinsthrombus while the PV group patients are susceptible to cardiovascular diseases.We evaluate the risk factors in JAK2V617F gene mutation positive patients andfind that these patients are at higher risk for vascular complications whencombined with an advanced age(＞60yrs), dyslipidemia, and white blood cellcount＞14.72×10~9/L, while the risk of thrombosis is not related to sexualdifference and smoking.