AbstractObjective: To analyze the DNA methylation gene mutations of myeloproliferative neoplasm (MPN), and preliminarily explore its clinical features.
Methods: Next-generation sequencing technology was used to detect 31 MPN-related genes in 105 cases of MPN patients ［40 cases of polycythaemia vera (PV), 65 cases of essential thrombocythemia (ET)］, and to analyze the relationship between DNA methylation gene mutations and clinical features.
Results: 15 mutation types were detected in 105 patients (88 mutations in total), and the total mutation detection rate was 87.6% (92/105). A total of 23 mutations in 4 DNA methylation genes (TET2, DNMT3A, IDH1, IDH2) were detected in 22 patients. The mutation rate of DNA methylation genes was 21.0%, mainly in the form of double mutations, including JAK2 V617F and TET2 (n=10), JAK2 V617F and DNMT3A (n=4), CALR and TET2 (n=2), JAK2 V617F and IDH1 (n=1). Compared with MPN patients without DNA methylation gene mutations, the proportion of women with DNA methylation gene mutations and the white blood cell count (WBC) were significantly higher (P<0.05). Compared with MPN patients with triple-negative driver genes, the proportion of women with DNA methylation gene mutations, age, WBC, platelet count (PLT), and neutrophil-to-lymphocyte ratio (NLR) were significantly higher (P<0.05). The remaining difference was not statistically significant (P>0.05). The MPN10 score, the incidence of thrombotic events, and the proportion of medium-risk and high-risk patients with DNA methylation gene mutations were significantly higher than those of MPN patients without DNA methylation gene mutations (P<0.05).
Conclusion: The mutation rate of DNA methylation genes was 21.0%, mainly coexisting in the form of double mutations. The proportion of women with DNA methylation gene mutations in MPN patients and WBC is high, the symptom load is heavy, the incidence of thrombosis is high, and the proportion of medium-high-risk patients is high, suggesting that their prognosis may be poor.
题目: 骨髓增殖性肿瘤患者DNA甲基化基因突变及临床特征分析.
目的: 分析骨髓增殖性肿瘤（MPN）患者DNA甲基化基因突变情况，初步探讨其临床特征.
方法: 采用二代测序技术检测105例MPN患者［真性红细胞增多症（PV）40例，原发性血小板增多症（ET）65例］的31种MPN相关基因，分析患者DNA甲基化基因突变与临床特征的关系.
结果: 105例患者中检出15种突变共88个突变，总突变检出率为87.6%（92/105）。22例患者检出4种DNA甲基化基因（TET2、DNMT3A、IDH1、IDH2）共23个突变。DNA甲基化基因突变率为21.0%，主要以双突变形式共存，包括JAK2 V617F和TET2（n=10）、JAK2 V617F和DNMT3A（n=4）、CALR和TET2（n=2）、JAK2 V617F和IDH1（n=1）。与无DNA甲基化基因突变的MPN患者相比，DNA甲基化基因突变的女性患者比例及白细胞数（WBC）显著升高（P<0.05）。与驱动基因三阴性的MPN患者相比，DNA甲基化基因突变的女性患者比例、年龄、WBC、血小板数（PLT）、中性粒细胞与淋巴细胞比值（NLR)均显著升高（P<0.05）。其余比较差异均无统计学意义（P>0.05）。DNA甲基化基因突变患者的MPN10评分、血栓事件发生率、中高危患者比例显著高于无DNA甲基化基因突变的MPN患者（P<0.05）.
结论: DNA甲基化基因突变率为21.0%，主要以双突变形式共存。DNA甲基化基因突变的MPN患者女性比例及WBC高，症状负荷重，血栓发生率高，中高危患者比例高，提示其预后可能较差.
Keywords: DNA methylation gene; clinical features; myeloproliferative neoplasm; next-generation sequencing technology.