The Clinical Implications of JAK2V617F Mutation in 137 Chinese Patients with Myeloproliferative Diseases.

Abstract A single acquired mutation in the JAK2 gene has recently been described in the classic myeloproliferative diseases(MPDs) including 65–97% of patients with polycythemia vera (PV), 23–57% of those with essential thrombocythemia (ET) and 35–57% of those with idiopathic myelofibrosis (IMF). The understanding of the molecular mechanisms has been considered a point mutation in exon 12 of the JAK2 gene, a key hematopoietic regulator, resulting in substitution of valine for phenylalanine at amino acid position 617 in the JH2 domain. In order to clarify the frequency and some clinical implication of JAK2V617F mutation in the Chinese patients with MPDs, we investigated this mutation in 137 Chinese patients aged 15 to 65 years. There are 57 patients with PV, 68 with ET, and 12 with IMF and the diagnosis of MPDs was defined according to published criteria. Genomic DNA samples obtained from all three MPDs and twenty cases of healthy people as negative control and the HEL, an erythroleukemic cell line, as positive control was screened by allele-specific PCR and gel electrophoresis for JAK2V617F mutation described by Baxter EJ et al. The results indicated that 65.69% of heterozygous JAK2V617F mutation was shown in 137 patients of over all MPDs, 73.68% in PV (42/57), 58.82% in ET (40/68), 66.67% in IMF (8/12). Sequence analysis of PCR products from selected patients confirmed existence of both mutant and wild-type alleles in patients with JAK2V617F mutation. A higher prevalence was observed in older patients with MPDs, and the WBC count of ET patients with JAK2V617F mutation is higher than that of ET patients without JAK2V617F mutation, and the difference has a statistical significance (P<0.05). The HGB concentration and platelet number of MPDs patients with JAK2V617F mutation were higher than those without JAK2V617F patients, but the difference did not achieve a statistical significance(P>0.05). Cytogenetic analyses were performed in 115 of the 137 MPDs patients. The chromosomal karyotype was normal in 108 of the 115 patients. Among them, JAK2V617F mutation was detected in 74 patients (68.51%) as compared with 5 of the 7 patients with karyotypic abnormalities (71.4%). Three patients with detective bcr/abl low expression assayed by FISH and real-time PCR techniques, two have JAK2V617F mutation. Our datas suggest that JAK2V617F mutation also occurs in a significant percentage of Chinese patients with the myeloproliferative diseases.