t(8;21)急性髓系白血病患者CSF3R基因突变及临床特征分析

Analysis of CSF3R Gene Mutations and Clinical Characteristics in Patients with t(8;21)Acute Myeloid Leukemia

目的:探讨t(8;21)急性髓系白血病(AML)患者CSF3R突变的发生情况及其与部分临床参数的相关性。方法:回顾性分析167例初诊伴有t(8;21)易位的AML患者的临床及实验室资料,采用高通量DNA测序技术联合Sanger测序法检测112种基因突变,分析CSF3R基因突变的发生情况及其对化疗后缓解率的影响。结果:167例t(8;21)易位的AML患者中,15例(9.0%)患者携带CSF3R突变,其中膜近端突变6例和胞质尾部截短突变9例。CSF3R最常见的共存突变依次为KIT(40.0%)、TET2(33.3%)、DNMT3A(26.7%)、FLT3(20.0%)、CBL(20.0%)、IDH1(13.3%)等。与野生型相比,CSF3R突变组具有更高的DNA甲基化基因突变发生率(P<0.001)。CSF3R基因突变阳性组患者初诊时外周血白细胞计数中位数为5.80(3.20-8.56)×109/L,显著低于CSF3R野生型组患者的8.80(5.26-19.92)×109/L(P=0.017);两组在性别、中位年龄、FAB分型、血红蛋白水平、血小板数等方面的差异均无统计学意义(P>0.05)。CSF3R基因突变组CR率(100%)虽高于野生组(86.8%),但差异无统计学意义(P>0.05)。CSF3R基因突变组患者CD19阳性率显著高于野生型组(86.7%vs 47.4%,P=0.004),且具有更高的X缺失伴随率(33.3%vs 13.2%,P=0.037)。结论:CSF3R突变在t(8;21)AML患者中有较高发生率,CSF3R突变阳性患者的临床特征及共存突变基因与野生型有所不同。

Objective:To investigate the occurrence of CSF3R mutation in patients with t(8;21)acute myeloid leukemia(AML)and its correlation with some clinical parameters.Methods:The clinical and laboratory data of 167 newly diagnosed AML patients with t(8;21)translocation were analyzed retrospectively.High-throughput DNA sequencing technology combined with Sanger sequencing method was used to detect 112 gene mutations.The occurrence of CSF3R gene mutation and its influence on the remission rate after chemotherapy were analyzed.Results:Among 167 patients with t(8;21)AML,15 patients(9.0%)carried CSF3R mutations,including 6 cases of membrane proximal region mutations and 9 cases of truncation mutations in the cytoplasmic tail.The most common coexisting mutations of CSF3R were KIT(40.0%),TET2(33.3%),DNMT3A(26.7%),FLT3(20.0%),CBL(20.0%),IDH1(13.3%),etc.Compared with the wild type,the CSF3R mutant group had a higher mutation rate of DNA methylation-related genes(P<0.001).The median peripheral white blood cell(WBC)count of patients with CSF3R gene mutation was 5.80(3.20-8.56)×10^(9)/L at initial diagnosis,which was significantly lower than 8.80(5.26-19.92)×10^(9)/L of the CSF3R wild-type patients(P=0.017).There was no significant difference between the two groups in sex,median age,FAB classification,hemoglobin level,platelet count,etc.(P>0.05).The CR rate of the CSF3R gene mutation group(100%)was significantly higher than that of the wild-type group(86.8%),but the difference was not statistically significant(P>0.05).The CSF3R gene mutation group had a significantly higher CD19 positive rate and a higher-X rate than the wild group(86.7%vs 47.4%,P=0.004;33.3%vs 13.2%,P=0.037).Conclusion:There is a high incidence of CSF3R mutation in t(8;21)AML patients.The clinical characteristics and coexisting mutation genes of CSF3R mutation-positive patients are different from those of wild-type patients.