117例骨髓增生异常综合征患者ASXL1基因突变的临床研究

ASXL1 gene mutation in 117 patients with myelodysplastic syndrome

目的探讨具有ASXL1分子学改变的骨髓增生异常综合征(myelodysplastic syndrome, MDS)患者的临床特点及预后。方法 117例MDS患者,采用第二代DNA测序技术检测骨髓中ASXL1基因突变情况,其中ASXL1基因突变34例为突变组,ASXL1基因未发现突变83例为未突变组;比较2组临床和实验室特征、患者生存时间以及对地西他滨治疗的有效率等。结果 117例MDS患者ASXL1基因突变率为29.06%,其中21例(61.76%)移码突变,9例(26.47%)点突变,4例(11.77%)无义突变;突变组难治性血细胞减少伴有多系增生异常比率(50.0%)高于未突变组(15.7%)(P<0.05),难治性贫血伴原始细胞增多2型比率(17.6%)低于未突变组(43.4%)(P<0.05),2组年龄、性别比例、染色体核型、骨髓原始细胞比例、白细胞计数、中性粒细胞计数、血小板计数和IPSS分层比较差异均无统计学意义(P>0.05);突变组生存时间[18.5(13.8,23.3)个月]短于未突变组[29.0(25.0,35.0)个月](P<0.05),对地西他滨治疗的有效率(77.7%)与未突变组(71.4%)比较差异无统计学意义(P>0.05)。结论 ASXL1移码突变比例高,ASXL1在难治性血细胞减少伴多系增生异常分型中突变率高,在难治性贫血伴原始细胞增多2型突变率低;ASXL1基因突变的MDS患者生存时间短,预后差。

Objective To investigate the clinical features and prognosis of patients with myelodysplastic syndrome(MDS) with ASXL1 molecular changes. Methods Totally 117 patients with MDS were detected ASXL1 mutation by next-generation sequencing technique and were divided into 34 patients with ASXL1 mutation(ASXL1-positive group) and 83 patients without ASXL1 mutation(ASXL1-negative group). The clinical and laboratory features, survival time and response to decitabine were compared between two groups. Results The ASXL1 gene mutation rate was 29.06% in 117 MDS patients, including 21 cases(61.76%) of frameshift mutation, 9 cases(26.47%) of point mutation, and 4 cases(11.77%) of nonsense mutation. The propotion of refractory cytopenia with multilineage dysplasin was significantly higher in ASXL1-positive group(50.0%) than that in ASXL1-negative group(15.7%)(P<0.05), the proportion of refractory anemia with excess blasts-2 was significantly lower in ASXL1-positive group(17.6%) than that in ASXL1-negative group(43.4%)(P<0.05), and there were no significant differences in the age, sex, karyotype, percentage of bone marrow blasts, white blood cell count, neutrophil count, platelet count and IPSS stratification between two groups(P>0.05). The survival time was significantly shorter in ASXL1-positive group(18.5(13.8, 23.3) months) than that in ASXL1-negative group(29.0(25.0, 35.0) months)(P<0.05), and there was no significant difference in the complete response rate to decitabine between ASXL1-postive group(77.7%) and ASXL1-negative group(71.4%)(P>0.05). Conclusion The proportion of ASXL1 frameshift mutation is high. The mutation rate of ASXL1 is high in patients with refractory cytopenia anemia with multidysplasia typing and is low in patients with refractory anemia with excess blasts-2. MDS patients with ASXL1 positive have short survival time and poor prognosis.