Background:Wide application of genome sequencing technologies has highlighted extensive genetic diversity in Acute Myeloid Leukemia (AML), yet the specific roles of individual genes remain unclear. This systematic review and meta-analysis aims to provide robust evidence for the prognostic impact of somatic gene mutations in de novo AML patients, while also exploring the prevalence of these mutations.Methods:Eligible studies were identified from PubMed and Scopus, with a focus on those reporting the prognostic influence of somatic gene mutations on overall survival (OS) or relapse-free survival (RFS) when compared to wild-type carriers. We calculated the pooled prevalence with 95% confidence intervals to assess the frequency of these mutations, and the pooled Hazard Ratio (HR) to compare OS and RFS associated with specific gene mutations.Results:We evaluated 53 somatic gene mutations using 80 studies, involving 20,048 de novo AML patients. The analysis revealed that the most prevalent affected genes were NPM1 (27%), DNMT3A (26%), and FLT3-ITD (24%). Mutations in CSF3R, TET2, and TP53 were significantly associated with poorer OS or RFS (p< 0.05). Sensitivity analysis confirmed that ASXL1, DNMT3A, and RUNX1 mutations were consistently linked to inferior OS or RFS. In contrast,CEBPAdmmutations were associated with favorable OS [HR = 0.39 (0.30–0.50)] and RFS [HR = 0.44 (0.37–0.54)]. Subgroup analysis showed that FLT3-ITD mutations were consistently associated with worse OS or RFS across all subgroups, though no significant subgroup differences were noted. No significant impact on OS or RFS was observed for mutations in GATA2, FLT3-TKD, KRAS, NRAS, IDH1, and IDH2.Conclusions:These findings provide critical insights into AML prognosis, aiding clinical decision-making and improving risk stratification strategies.
背景：基因组测序技术的广泛应用揭示了急性髓系白血病（AML）中广泛的遗传多样性，但单个基因的具体作用仍不明确。本系统综述与荟萃分析旨在为新发AML患者体细胞基因突变的预后影响提供有力证据，同时探讨这些突变的流行情况。 方法：通过PubMed和Scopus数据库筛选符合条件的研究，重点关注报告体细胞基因突变对总生存期（OS）或无复发生存期（RFS）预后影响并与野生型携带者进行比较的文献。我们计算了合并患病率（95%置信区间）以评估这些突变的频率，并计算合并风险比（HR）以比较特定基因突变相关的OS和RFS。 结果：我们通过80项研究评估了53个体细胞基因突变，共涉及20,048例新发AML患者。分析显示，最常见的突变基因包括NPM1（27%）、DNMT3A（26%）和FLT3-ITD（24%）。CSF3R、TET2和TP53突变与较差的OS或RFS显著相关（p<0.05）。敏感性分析证实，ASXL1、DNMT3A和RUNX1突变始终与较差的OS或RFS相关。相比之下，CEBPA双等位基因突变与良好的OS[HR=0.39（0.30–0.50）]和RFS[HR=0.44（0.37–0.54）]相关。亚组分析显示，FLT3-ITD突变在所有亚组中均与较差的OS或RFS相关，但未观察到显著的亚组间差异。GATA2、FLT3-TKD、KRAS、NRAS、IDH1和IDH2突变对OS或RFS未显示出显著影响。 结论：这些发现为AML预后提供了重要见解，有助于临床决策并改善风险分层策略。
肿瘤(癌症)患者之家