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U2AF1 突变对初发骨髓增生异常综合征患者预后的价值:一项荟萃分析。

Prognostic value of U2AF1 mutant in patients with de novo myelodysplastic syndromes: a meta-analysis.

机构信息

Department of Hematology, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China.

出版信息

Ann Hematol. 2019 Dec;98(12):2629-2639. doi: 10.1007/s00277-019-03843-3. Epub 2019 Nov 21.

Abstract

U2 small nuclear RNA auxiliary factor 1 (U2AF1) mutant is the most common molecular biological abnormality in patients with myelodysplastic syndromes. Some studies have reported the prognostic impact of U2AF1 mutant in patients with de novo MDS, with discrepant results, so we do a meta-analysis about the relevant literatures to further investigate their prognostic impact on patients with de novo MDS. We conducted a literature search on databases such as PubMed, Embase, and the Cochrane Library to obtain studies on the prognosis of U2AF1 mutant in patients with de novo MDS published up to August 9, 2018. The primary endpoint was overall survival (OS), and the secondary endpoint was acute myeloid leukemia (AML) transformation. We extracted the hazard ratios (HRs) of OS and AML transformation and their 95% confidence intervals (CIs). Meta-analysis was performed by selecting a fixed-effect model or a random-effects model based on the heterogeneity between studies. A total of 14 cohort studies were included in the final meta-analysis, including 3322 patients with de no MDS, in which 390 patients were associated with U2AF1 mutant. The results showed that U2AF1 mutant had an adverse prognostic impact on OS (HR = 1.84, 95% CI: 1.45-2.33, P < 0.00001) and AML transformation (HR = 2.47, 95% CI: 1.50-4.06, P = 0.0004). U2AF1 mutant was associated with shorter OS in subgroup analyses of low- or intermediate-1-IPSS, U2AF1 and U2AF1. Out meta-analysis indicates that U2AF1 mutants are independent, detrimental prognostic factors for OS and AML transformation in patients with de novo MDS, as well as associating with shorter OS in subgroups of low- or intermediate-1-IPSS, U2AF1 and U2AF1. Further prospective studies are needed in the future, and subgroup analysis of U2AF1 subgroups is needed to obtain a more reliable basis for the impact of U2AF1 mutant on the prognosis of de novo MDS.

摘要

U2 小核 RNA 辅助因子 1(U2AF1)突变是骨髓增生异常综合征患者中最常见的分子生物学异常。一些研究报道了 U2AF1 突变对初发性 MDS 患者的预后影响,但结果存在差异,因此我们对相关文献进行了荟萃分析,以进一步探讨 U2AF1 突变对初发性 MDS 患者的预后影响。我们在 PubMed、Embase 和 Cochrane Library 等数据库中进行了文献检索,以获取截至 2018 年 8 月 9 日发表的关于 U2AF1 突变对初发性 MDS 患者预后影响的研究。主要终点是总生存期(OS),次要终点是急性髓系白血病(AML)转化。我们提取了 OS 和 AML 转化的风险比(HR)及其 95%置信区间(CI)。根据研究之间的异质性,选择固定效应模型或随机效应模型进行荟萃分析。最终荟萃分析纳入了 14 项队列研究,共包括 3322 例初发性 MDS 患者,其中 390 例患者伴有 U2AF1 突变。结果显示,U2AF1 突变对 OS(HR=1.84,95%CI:1.45-2.33,P<0.00001)和 AML 转化(HR=2.47,95%CI:1.50-4.06,P=0.0004)均有不良预后影响。在低危或中危-1-IPSS、U2AF1 和 U2AF1 亚组分析中,U2AF1 突变与较短的 OS 相关。本荟萃分析表明,U2AF1 突变是初发性 MDS 患者 OS 和 AML 转化的独立、不良预后因素,并且与低危或中危-1-IPSS、U2AF1 和 U2AF1 亚组的较短 OS 相关。未来需要进一步进行前瞻性研究,并对 U2AF1 亚组进行亚组分析,以获得 U2AF1 突变对初发性 MDS 患者预后影响的更可靠依据。

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