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。

abstractsObjective: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 patients with mutations in genes related to chromatin modifications.