儿童急性髓系白血病的核磷酸蛋白基因突变研究

目的 检测儿童急性髓系白血病(AML)患者的核磷酸蛋白(NPM1)基因突变,研究NPM1基因突变在患者中的特点和临床意义.方法 采用高分辨率熔解曲线(HRM)分析法得出样本中NPMI基因突变情况,分析NPM1基因突变与儿童AML患者的临床表现和预后的关系.结果 70例初诊儿童AML患者NPM1突变率为45.7%.NPM1突变组外周血血小板计数明显高于NPM1野生组(P=0.013).正常核型组与异常核型组突变率差异无统计学意义(P>0.05).AML-ETO或PMLRARα融合基因阳性组突变率低于融合基因阴性组(P=0.048).与NPM1野生组相比,NPM1突变组相对缓解率、5年无事件生存(EFS)率、5年总体生存(OS)率相对较高,但两组差异无统计学意义(P值分别为0.217、0.374、0.380).结论 该组病例中,NPM1基因突变阳性率较高.NPM1突变组和NPM1野生组在临床各项指标的差异不大,NPM1突变组的预后相对较好,但两组的差异无统计学意义.

Study on NPM1 gene mutations in childhood acute myeloid leukemia

Objective To examine the incidence and clinical significance of NPM1 mutations in childhood acute myeloid leukemia( AML) patients. Methods NPM1 mutations of 70 newly diagnosed childhood AML were detected by high resolution melting( HRM) analysis on the LightCycler 480. The incidence and clinical significance were analyzed. Results NPM1 mutations were identified in 32 (45.7% ) of the 70 AML children. There was no significant difference in clinical characteristics between patients with or without NPM1 mutation, but patients with NPM1 mutation had a higher platelet count (P = 0.013). There was also no significant difference in NPM1 mutation between normal and abnormal karyotype groups. In AML-ETO or PML-RARα positive groups, the incidence of NPM1 mutations was significant lower(P= 0.048). There was no significant difference in response rates after induction therapy (P =0. 217), but the complete remission (CR) rate was higher in the NPM1 -mutated group (81.3% ). There was a trend toward higher event-free survival (EFS) and overall survival (OS) rates in the NPM1 mutated patients than that in wild NPM1 patients (EFS=53.8% vs 41.4% , OS =52.7% vs 39. 2% ), but the difference was not statistically significant P = 0. 374 and 0. 380). Conclusion NPM1 mutations were relatively common in our cohort of AML patients. There was no significant difference in clinical characteristics between patients with and without NPM1 mutation. The NPM1 mutation patients group seemed to have better therapy response, but the difference was not statistically significant.