NRAS基因突变在成人正常核型急性髓系白血病中的临床特征及疗效分析

Clinical characteristics and therapeutic efficacy of NRAS mutation in adults with cytogenetically acute myeloid leukemia

目的研究成人正常核型急性髓系白血病(cytogenetically normal acute myeloid leukemia,CN-AML)患者NRAS基因的突变情况、临床特征及其对疗效的影响。方法利用二代测序技术联合Sanger测序检测2016年至今江南大学附属医院、常州市第二人民医院住院及门诊治疗的初诊CN-AML患者166例基因突变,包括NRAS,NPM1,FLT3-ITD,KRAS,DNMT3A,RUNX1等51种基因。结果166例初发CN-AML患者中,NRAS基因突变率为15.1%。NRAS突变多发生在M5型(P<0.05),但在年龄、性别、白细胞计数、血红蛋白、血小板计数方面差异无统计学意义(P>0.05)。NRAS突变组的完全缓解率(complete remission,CR)与无NRAS突变组相比,差异有统计学意义(P<0.05)。当NRAS伴有NPM1、FLT3-ITD、DNMT3A、RUNX1时,突变组与野生组比较,CR率差异无统计学意义(P>0.05)。结论NRAS突变在CN-AML中多发生于M5型,均伴有额外的基因突变,首次诱导治疗后CR率高。

Objective To investigate the mutational features,clinical characteristics and therapeutic effects of NRAS in adults with cytogenetically normal acute myeloid leukemia(CN-AML).Methods Second-generation sequencing and Sanger sequencing were used to detect 51 gene mutations from 166 patients which were newly diagnosed CN-AML patients hospitalized and outpatient in the third affiliated hospital of Nantong university and Changzhou second people’s hospital from2016 to now,including NRAS,NPM1,FLT3-ITD,KRAS,DNMT3 A,RUNX1 and so on.Results Among 166 patients with primary CN-AML,the mutation rate of NRAS was 15.1%.NRAS mutations occurred mostly in M5 subtype(P<0.05),but there was no significant difference in age,gender,white blood cell count,hemoglobin,and platelet count(P>0.05).Compared with the group without NRAS mutation,the complete remission(CR)rate of the NRAS mutation group was statistically different(P<0.05).There was no significant difference in CR rate between the patients with NPM1,FLT3-ITD,DNMT3 A and RUNX1 mutations and the wide type.(P>0.05).Conclusion The mutation rate of NRAS in CN-AML was as high as 15.1%,mostly occurring in M5 subtype.All of them coexisted with additional gene mutations and had a high CR rate after the first induction therapy.