Prognostic significance of ASXL1 mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia: A meta-analysis
Prognostic significance of ASXL1 mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia: A meta-analysis
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ASXL1 突变在骨髓增生异常综合征和慢性粒单核细胞白血病中的预后意义：一项荟萃分析
DOI：
10.1080/10245332.2015.1106815
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发表时间：
2016-01-01
期刊：
影响因子：
1.9
通讯作者：
Wang, Shao-Yuan
中科院分区：
文献类型：
--
作者：
Lin, Yun;Zheng, Yi;Wang, Shao-Yuan
目的：虽然长期以来在骨髓增生异常综合征 (MDS) 和慢性粒单核细胞白血病 (CMML) 中存在额外的性梳状 1 (ASXL1) 基因突变，但其预后意义一直存在争议。因此，研究 ASXL1 突变对 MDS 和 CMML 患者影响的荟萃分析是有用的。方法：从一些常见数据库中检索识别出的文章。我们提取了总生存期 (OS) 和无白血病生存期 (LFS) 的风险比 (HR) 以及一些临床参数的 P 值，将 AXSL1 突变与现有研究中未突变的突变进行比较。每个单独的 HR 和 P 值用于计算汇总的 HR 和 P 值。结果：本次荟萃分析选择了六项涵盖 1689 名患者的研究。 OS 和 LFS 的汇总 HR 分别为 1.45（95% 置信区间 (CI)，1.24–1.70）和 2.20（95% CI，1.53–3.17）。当单独考虑 CMML 患者时，OS 的 HR 为 1.50（95% CI，1.18-1.90）。此外，ASXL1突变更常见于男性（P = 0.008）、老年人（P = 0.019）和血小板（P = 0.009）或血红蛋白水平（P = 0.0015）较低的患者，并与其他突变如EZH2、IDH1/2、RUNX1和TET2相关。讨论：尽管我们的分析有其局限性，但它表明 ASXL1 突变对法国、美国、英国定义的 MDS 患者的 OS 和 LFS 的影响显着较差。然而，不同类型的ASXL1突变对MDS患者的影响仍需阐明。结论：ASXL1 突变与 MDS 不良预后相关，这可能有助于该疾病的风险分层和预后评估。
Objectives: Although additional sex comb-like 1 (ASXL1) gene mutations have long been reported in myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML), the prognostic significance has been controversial. Therefore, a meta-analysis to study the impact of ASXL1 mutations on patients with MDS and CMML is useful. Methods: The identified articles were retrieved from some common databases. We extracted hazard ratios (HRs) for overall survival (OS) and leukemic-free survival (LFS) and P-value of some clinical parameters, which compared AXSL1 mutations to those without from the available studies. Each individual HR and P-value was used to calculate the pooled HR and P-value. Results: Six studies covering 1689 patients were selected for this meta-analysis. The pooled HRs for OS and LFS were 1.45 (95% confidential interval (CI), 1.24–1.70) and 2.20 (95% CI, 1.53–3.17), respectively. When considering CMML patients alone the HR for OS was 1.50 (95% CI, 1.18–1.90). Additionally, ASXL1 mutations were more frequently found in male (P = 0.008), older (P = 0.019), and patients with lower platelets (P = 0.009) or hemoglobin level (P = 0.0015) and associated with other mutations such as EZH2, IDH1/2, RUNX1, and TET2. Discussion: Although our analysis has its limitation, it showed that ASXL1 mutations had significant inferior impact on OS and LFS for French–American–British-defined MDS patients. However, the influence of different types of ASXL1 mutations on patients with MDS still needs illustrating. Conclusion: ASXL1 mutations were associated with poor prognosis in MDS, which may contribute to risk stratification and prognostic assessment in the disease.