Department of Haematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, China.
Int J Lab Hematol. 2010 Aug 1;32(4):381-6. doi: 10.1111/j.1751-553X.2009.01208.x. Epub 2010 Mar 23.
Recent studies have shown that JAK2 V617F, MPL W515L/K and JAK2 exon 12 mutations underlie the major molecular pathogenesis of myeloproliferative disorders (MPN). Allele-Specific Polymerase Chain Reaction (AS-PCR), direct sequencing and MassARRAY assay were used to ascertain the real prevalence of these mutations and the influence of genetic susceptibility in Chinese MPN patients. The positive rate of JAK2 V617F in polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) was 82.0%, 36.6% and 51.1% respectively. One ET patient and two PMF patients harboured the MPL W515L mutation and three PV patients harboured JAK2 exon 12 mutations. All of these patients were confirmed as JAK2 V617F negative. Clinical data demonstrated that PV patients with JAK2 exon 12 mutations were younger, had higher haemoglobin levels and white blood cell counts than PV patients with JAK2 V617F. In addition, through analysis of 4 polymorphic loci of JAK2 gene, no significant difference of distribution frequency was found among PV, ET and PMF patients. Distribution frequency of haplotype also was not significantly different among PV, ET and PMF patients. We conclude that JAK2 V617F is a major molecular pathogenesis in Chinese MPN patients. MPL W515L mutation and JAK2 exon 12 mutations can also be found in JAK2 V617F negative MPN patients.
最近的研究表明，JAK2 V617F、MPL W515L/K 和 JAK2 外显子 12 突变是骨髓增殖性疾病（MPN）的主要分子发病机制。等位基因特异性聚合酶链反应（AS-PCR）、直接测序和 MassARRAY 检测法用于确定这些突变的真实流行率以及遗传易感性在中国 MPN 患者中的影响。JAK2 V617F 在真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）中的阳性率分别为 82.0%、36.6%和 51.1%。一名 ET 患者和两名 PMF 患者存在 MPL W515L 突变，三名 PV 患者存在 JAK2 外显子 12 突变。所有这些患者均被确认为 JAK2 V617F 阴性。临床数据表明，JAK2 外显子 12 突变的 PV 患者比 JAK2 V617F 的 PV 患者更年轻，血红蛋白水平和白细胞计数更高。此外，通过对 JAK2 基因的 4 个多态性位点进行分析，在 PV、ET 和 PMF 患者中未发现分布频率有显著差异。PV、ET 和 PMF 患者之间的单倍型分布频率也没有显著差异。我们的结论是，JAK2 V617F 是中国 MPN 患者的主要分子发病机制。在 JAK2 V617F 阴性的 MPN 患者中也可以发现 MPL W515L 突变和 JAK2 外显子 12 突变。
