The Investigation And Clinical Significance Of JAK2V617F Mutation In Myeloproliferative Neoplasm Patients

Objective: To explore the occurrence of JAK2V617F mutation in myeloproliferative neoplasm patients ,especially the positivity rates in various MPN with negative BCR-ABL fusion gene. Combined with the clinical date and laboratory investigation , to study the significance of JAK2V617F mutation for supervision, evaluation and prognosis.Method: Genomic DNA samples extracted from bone marrow or blood monocular cells, Allele-specific polymerase chain reaction (AS-PCR) was used to amplify the exon 12 of JAK2 gene which harbours V617F mutation. The study cohort comprised 108 myeloproliferative neoplasm (MPN) cases, including 41 cases with chronic myeloid leukemia (CML), 24 cases with Polycythemia Vera (PV),29 cases with essential thrombocythemia (ET) ,8 cases with primary myelofibrosis(PMF) , 2case with hypereosinophilia syndrome (HES) ,and 1 case with myeloproliferative neoplasm, unclassifiable (MPN-U).Meanwhile 15 patients , which were subdivided into groups of 5 cases of lymphoma, 5 cases of acute leukemia, 3 cases of myelodysplastic syndrome and 2 cases of aplastic anemia ,and 10 healthy blood donors were selected as the disease control group and the normal control group, respectively. The relevance of JAK2V617F mutation in different groups and the clinical and laboratory data was analyzed. All data was analyzed by statistical software SPSS13.0;Results: JAK2V671F mutation was detected in 21 of the 24 patients with PV (87.5%), 15 of the 29 with ET (51.7%) and 4of the 8 with PMF (50.0%). The positive rate in MPN patients with negative BCR-ABL fusion gene was 62.5%(40/64), however, none of CML patients with positive BCR-ABL fusion gene and control groups had JAK2V671F mutation (P<0.05). The positive rate of Ph chromosome of all CML was 100% by conventional chromosomal analysis; whether JAK2V671F mutation or not , all MPN with negative BCR-ABL fusion gene were detected in normal karyotype . PV patients with JAK2V617F positive were older and had more leukocytes than the negative patients. (P<0.05), while ET patients with JAK2V617F positive have more leukocytes, higher hemoglobin levels and thromboembolism than JAK2V617F negative patients(P<0.05). The occurrences of thromboembolism in MPN with negative BCR-ABL fusion gene with JAK2V617F positive were more than that of JAK2V617F negative group (P<0.05).Conclusions: In addition to bone marrow, BCR-ABL fusion gene and chromosome examinations, JAK2V617F mutation can be used as a routine index in suspected or diagnostic MPN patients. Allele-specific polymerase chain reaction (AS-PCR) can detect JAK2V617F mutation effectively , especially in the various MPN with negative BCR-ABL fusion gene. There are significant differences between JAK2V617F positive and the negative in leukocytes levers of the various MPN patients with negative BCR-ABL fusion gene. The results suggest that a certain correlation may exist between JAK2V617F mutation and leukocytes level. The chromosome karyotype of all MPN patients with negative BCR-ABL fusion gene was normal, so the correlation of the two has to be further explored. Patients with JAK2V617F positive have more susceptible to thrombosis than JAK2 negative patients with negative BCR-ABL fusion gene. JAK2V617F positive might be considered to be a risk factor that affects the occurrence of thromboembolism, so it must be paid enough attention.