伴NRAS基因突变的急性髓系白血病患者的临床特征及生存分析

目的:探讨伴有NRAS基因突变的急性髓系白血病(acute myeloid leukemia,AML)患者的临床特征及生存分析。方法:回顾性分析2016年05月至2019年12月就诊于空军军医大学唐都医院血液内科的225例初诊AML患者的临床资料,采用二代测序技术进行基因突变检测,分析NRAS基因突变患者的临床特征并进行预后分析。结果:共有36例(16%)患者检测到NRAS基因突变,全部为错义突变,33例突变位点位于2号外显子12、13号密码子,2例位于3号外显子61号密码子,1例位于4号外显子109密码子。中位突变比例为21.99%(1%~49.85%)。伴有NRAS基因突变的患者中位年龄为44(9~85)岁。年龄分布、前期血液病史、初诊时外周血细胞计数、骨髓原始细胞比例等与无NRAS患者差异相比均无统计学意义。伴有NRAS突变组的患者一疗程诱导化疗完全缓解率高于NRAS野生型组(P=0.033),但复发率也较高(P=0.055)。伴NRAS基因突变组患者的中位OS时间为22个月,无NRAS基因突变组患者的中位OS时间为28个月,两组OS时间无统计学差异(P=0.485);两组患者的RFS时间存在统计学差异(P=0.036)。采用“3+7”方案诱导治疗的患者中位OS时间40个月,8例采用DEC+CAG方案诱导化疗的患者中位OS时间为15个月(P=0.027)。36例患者中31例伴有其他基因突变,生存分析显示NRAS同时伴DNMT3A突变组患者的预后更差(P=0.019)。结论:AML患者NRAS突变率16%,均为错义突变,大部分位于2号外显子12、13号密码子。伴有NRAS突变的患者CR率高,复发率也高,RFS时间短于无NRAS突变组。“3+7”方案诱导治疗缓解率更高。NRAS伴DNMT3A突变提示预后差。

Clinical characteristics and survival analysis of acute myeloid leukemia patients with NRAS gene mutation

Objective:To investigate the clinical features and survival analysis of acute myeloid leukemia(AML) patients with NRAS gene mutation.Methods:The clinical data of 225 newly diagnosed AML patients who visited the department of hematology,our hosptial from May 2016 to December 2019 were retrospectively analyzed.Next-generation sequencing technology was used for gene mutation detection,and the clinical characteristics and prognosis of patients with NRAS gene mutation were analyzed.Results:A total of 36 patients(16%) were found to have NRAS gene mutations,all of them belonged to missense mutations.30 case of mutations occurred at codons 12 and 13 of exon 2,and 2 case of mutations occurred at codon 61 of exon 3,1 case occurred at codon 109 of exon 4.The median mutation rate was 21.99%(1%~49.85%).The median age of patients with NRAS mutations was 44 (9~85) years.There were no significant differences in age distribution,previous blood history,peripheral blood cell count at initial diagnosis,and proportion of bone marrow blasts compared with patients without NRAS.The complete remission rate of patients with NRAS mutation group was higher than that of NRAS wild-type group after one course of induction chemotherapy (P=0.033),however,the recurrence rate was also higher in NRAS mutation group (P=0.055).The median OS time of patients with NRAS gene mutation was 22 months,and the median OS time of patients without NRAS gene mutation was 28 months.There was no statistical difference in OS time between these two groups (P=0.485),however,there was a statistically significant difference in RFS time between the two groups (P=0.036).The median OS time of patients treated with "3+7" regimen was 40 months,the median OS time of 8 patients treated with "DEC+CAG" regimen was 15 months (P=0.027).31 patients with NRAS gene mutation had other gene mutations,and survival analysis showed that the prognosis of patients with NRAS and DNMT3A mutation was much worse(P=0.019).Conclusion:The NRAS mutation rate in AML patients is 16%,all of which are missense mutations,most of which occur at codons 12 and 13 of exon 2.Patients with NRAS mutation have higher CR rate,but higher recurrence rate and shorter RFS time than those without NRAS mutation.The "3+7" regimen induces a higher remission rate in patients with NRAS mutation.NRAS with DNMT3A mutation is associated with poor prognosis.