DataSheet_1_Impact of mutations in epigenetic modifiers in acute myeloid leukemia: A systematic review and meta-analysis.pdf

This is a systematic review and meta-analysis evaluating the prognostic significance of epigenetic mutations on the overall survival (OS) in Acute Myeloid Leukemia (AML). We searched for studies evaluating epigenetic mutations in AML (up to November 2018) in PubMed, Trip database and Cochrane library. Hazard ratio (HR) of outcomes were extracted, and random-effects model was used to pool the results. A total of 10,002 citations were retrieved from the search strategy; 42 articles were identified for the meta-analysis (ASXL1 = 7, TET2 = 8, DNMT3A = 12, IDH =15), with fair to good-quality studies. The pooled HR was 1.88 (95% CI: 1.49−2.36) for ASXL1 mutation, 1.39 (95% CI: 1.18−1.63) for TET2 mutation, 1.35 (95% CI 1.16-1.56) for DNMT3a and 1.54 (95% CI: 1.15-2.06) for IDH mutation. However, there was a substantial heterogeneity in the DNMT3a and IDH studies. In conclusion epigenetic mutations in ASXL1, TET2, DNMT3a and IDH adversely impact OS in patients with AML albeit with considerable heterogeneity and possibly publication bias. Further studies are required to address these limitations.

本研究为一项系统评价与荟萃分析，旨在评估表观遗传突变对急性髓系白血病（Acute Myeloid Leukemia, AML）患者总生存期（overall survival, OS）的预后价值。我们于PubMed、Trip数据库及Cochrane图书馆中检索了2018年11月之前发表的、针对急性髓系白血病患者表观遗传突变的相关研究。研究提取了结局指标的风险比（hazard ratio, HR），并采用随机效应模型对研究结果进行合并分析。本次检索策略共检索到10002篇文献，最终纳入42篇中等至高质量的研究开展荟萃分析，其中涉及ASXL1突变相关研究7项、TET2突变相关研究8项、DNMT3A突变相关研究12项、IDH突变相关研究15项。合并后的风险比结果显示：ASXL1突变的HR为1.88（95%置信区间：1.49−2.36），TET2突变的HR为1.39（95%置信区间：1.18−1.63），DNMT3A突变的HR为1.35（95%置信区间：1.16−1.56），IDH突变的HR为1.54（95%置信区间：1.15−2.06）。然而，DNMT3A与IDH相关研究存在显著异质性。综上，ASXL1、TET2、DNMT3A及IDH相关的表观遗传突变会对急性髓系白血病患者的总生存期产生不良影响，但此类研究存在较大异质性，且可能存在发表偏倚。需开展进一步研究以解决上述局限性。