摘要
目的评价基于二代测序(NGS)检测技术下的克隆性基因突变对核心结合因子相关急性髓系白血病(CBF-AML)预后的影响。方法回顾性分析2011年7月至2017年8月在苏州大学附属第一医院血液科诊治的195例成人初治CBF-AML患者,其中诱导化疗达完全缓解的患者190例,包括134例RUNX1-RUNXIT1+AML和56例CBFβ-MYH11+AML,年龄15~64岁,中位随访时间43.6个月。采用Log-rank检验和Cox回归模型分析临床因素和基因突变对患者总生存(OS)和无病生存(DFS)的影响。结果在195例患者中,KIT基因突变发生率最高(47.6%),其次为NRAS(20.0%)、FLT3(18.4%)、ASXL2(14.3%)、KRAS(10.7%)、ASXL1(9.7%)。按基因功能分类,酪氨酸激酶信号通路基因突变发生率最高(76.4%),其次为染色质修饰相关基因(29.7%)。在接受强化巩固治疗的患者中,CBFβ-MYH11+AML患者的OS有优于RUNX1-RUNXIT1+AML患者的趋势(P=0.062)。染色质修饰相关基因突变仅在RUNX1-RUNXIT1+AML中检出,但对患者的DFS无明显影响(P=0.557)。染色质修饰相关基因突变阳性且接受异基因造血干细胞移植(allo-HSCT)的患者预后最好。多因素分析显示KIT exon17突变为影响RUNX1-RUNXIT1+AML患者DFS的独立危险因素(P<0.001),allo-HSCT能明显改善RUNX1-RUNXIT1+AML患者的DFS(P=0.010)。结论合并KIT exon17突变的RUNX1-RUNXIT1+AML患者预后差,allo-HSCT可改善这部分患者的预后,allo-HSCT也能使染色质修饰相关基因突变阳性患者的预后得到改善。
Objective To evaluate the prognostic significance of clonal gene mutations using next-generation sequencing in patients with core-binding factor acute myeloid leukemia(CBF-AML)who achieved first complete remission after induction chemotherapy.Methods The study,which was conducted from July 2011 to August 2017 in First Affiliated Hospital of Soochow University,comprised 195 newly diagnosed patients with CBF-AML,including 190 patients who achieved first complete remission after induction chemotherapy.The cohort included 134 patients with RUNX1-RUNXIT1+AML and 56 patients with CBFβ-MYH11+AML.The cohort age ranged from 15 to 64 years,with a median follow-up of 43.6 months.Overall survival(OS)and disease-free survival(DFS)were assessed by the log-rank test,and the Cox proportional hazards regression model was used to determine the effects of clinical factors and genetic mutations on prognosis.Results The most common genetic mutations were in KIT(47.6%),followed by NRAS(20.0%),FLT3(18.4%),ASXL2(14.3%),KRAS(10.7%),and ASXL1(9.7%).The most common mutations involved genes affecting tyrosine kinase signaling(76.4%),followed by chromatin modifiers(29.7%).Among the patients receiving intensive consolidation therapy,the OS tended to be better in patients with CBFβ-MYH11+AML than in those with RUNX1-RUNXIT1+AML(P=0.062).Gene mutations related to chromatin modification,which were detected only in patients with RUNX1-RUNXIT1+AML,did not affect DFS(P=0.557).The patients with mutations in genes regulating chromatin conformation who received allo-hematopoietic stem cell transplantation(allo-HSCT)achieved the best prognosis.Multivariate analysis identified KIT exon 17 mutations as an independent predictor of inferior DFS in patients with RUNX1-RUNXIT1+AML(P<0.001),and allo-HSCT significantly prolonged DFS in these patients(P=0.010).Conclusions KIT exon 17 mutations might indicate poor prognosis in patients with RUNX1-RUNXIT1+AML.Allo-HSCT may improve prognosis in these patients,whereas allo-HSCT might also improve prognosis in pat
作者
吴天梅
薛胜利
李正
于景秋
王隽
王斌儒
万超玲
申向东
邱桥成
鲍协炳
吴德沛
Wu Tianmei;Xue Shengli;Li Zheng;Yu Jingqiu;Wang Jun;Wang Binru;Wan Chaoling;Shen Xiangdong;Qiu Qiaocheng;Bao Xiebing;Wu Depei(The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,National Clinical Research Center for Hematologic Diseases,NHC Key Laboratory of Thrombosis and Hemostasis,Suzhou 215006,China)
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2021年第8期646-653,共8页
Chinese Journal of Hematology
基金
国家自然科学基金(81970138)
国家血液系统疾病临床医学研究中心转化研究课题(2020ZKMB05)
江苏省"333工程"人才项目(BRA2018391)
江苏省青年医学人才项目(QNRC2016719)
姑苏卫生人才项目(GSWS2019007)。
