The Prognostic Value of TP53 Mutations in Adult Acute Myeloid Leukemia: A Meta-Analysis.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2023-06-01 DOI:10.1159/000526174

Guoxiang Qin, Xueling Han

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引用次数: 2

Abstract

Objective: Mutations of the tumor protein p53 (TP53) gene were considered to be associated with an unfavorable prognosis in acute myeloid leukemia (AML). This meta-analysis aimed to systematically elucidate the prognostic value of TP53 mutation in adult patients with AML.

Method: A comprehensive literature search was conducted for eligible studies published before August 2021. The primary endpoint was overall survival (OS). Pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated for prognostic parameters. Subgroup analyses based on intensive treatment were performed.

Results: Thirty-two studies with 7,062 patients were included. As compared to wild-type carriers, AML patients with TP53 mutations had significantly shorter OS (HR: 2.40, 95% CI: 2.16-2.67, I²: 46.6%). Similar results were found in DFS (HR: 2.87, 95% CI: 1.88-4.38), EFS (HR: 2.56, 95% CI: 1.97-3.31), and RFS (HR: 2.40, 95% CI: 1.79-3.22). Mutant TP53 predicted inferior OS (HR: 2.77, 95% CI: 2.41-3.18) in the intensively treated AML subgroup, compared with the non-intensively treated group (HR: 1.89, 95% CI: 1.58-2.26). Among intensively-treated AML patients, the age of 65 did not affect the prognostic value of TP53 mutations. Besides, TP53 mutation was also strongly associated with an elevated risk of adverse cytogenetics, which conferred a dismal OS in AML patients (HR: 2.03, 95% CI: 1.74-2.37).

Conclusion: TP53 mutation exhibits a promising potential for discriminating AML patients with a worse prognosis, thus being capable of serving as a novel tool for prognostication and therapeutic decision-making in the management of AML.

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TP53突变在成人急性髓性白血病中的预后价值:一项荟萃分析。

目的:肿瘤蛋白p53 (TP53)基因突变被认为与急性髓性白血病(AML)的不良预后有关。这项荟萃分析旨在系统地阐明TP53突变在成年AML患者中的预后价值。方法:对2021年8月前发表的符合条件的研究进行综合文献检索。主要终点是总生存期(OS)。计算预后参数的合并风险比(hr)及其95%置信区间(ci)。以强化治疗为基础进行亚组分析。结果:纳入32项研究，7062例患者。与野生型携带者相比，TP53突变的AML患者OS明显缩短(HR: 2.40, 95% CI: 2.16-2.67, I2: 46.6%)。在DFS (HR: 2.87, 95% CI: 1.88-4.38)、EFS (HR: 2.56, 95% CI: 1.97-3.31)和RFS (HR: 2.40, 95% CI: 1.79-3.22)中也发现了类似的结果。与非强化治疗组(HR: 1.89, 95% CI: 1.58-2.26)相比，强化治疗的AML亚组突变体TP53预测较差的OS (HR: 2.77, 95% CI: 2.41-3.18)。在强化治疗的AML患者中，65岁不影响TP53突变的预后价值。此外，TP53突变也与不良细胞遗传学风险升高密切相关，这使得AML患者的OS很低(HR: 2.03, 95% CI: 1.74-2.37)。结论:TP53突变在鉴别预后较差的AML患者方面具有良好的潜力，因此可以作为AML治疗中预测和治疗决策的新工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.