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Downregulation of p21 in myelodysplastic syndrome is associated with p73 promoter hypermethylation and indicates poor prognosis.

在骨髓增生异常综合征中,p21基因的下调与p73基因启动子甲基化有关,并提示预后不良。

Zhao Y,Guo J,Zhang X,Zhang Z,Gu S,Fei C,Li X,Chang C

Abstract

p21 Can both promote and inhibit tumorigenic processes. We explored the role of p21 in myelodysplastic syndrome (MDS).
In this study, we analyzed p21 expression and p73 methylation in 88 patients with de novo MDS.
We found decreased expression of the p21 gene in higher-risk MDS compared with lower-risk groups or healthy controls (P < .05). Patients with p73 methylation had lower p21 than those in the unmethylated group (P < .001). Moreover, there was a significantly positive correlation between p73 and p21 expression in MDS (r = 0.436, P < .001). In vitro assays further confirm the role of p73 methylation in p21 expression. Compared with patients with normal expression levels of p21, patients with lower p21 expression levels experienced much higher rates of transformation to acute myeloid leukemia and lower overall survival both in univariate as well as multivariate analyses.
Our results suggest p21 expression may serve as a new biomarker to predict clinical outcome in patients with MDS.

摘要

P21可以同时促进和抑制肿瘤发生的过程。我们研究p21基因在骨髓增生异常综合征(MDS)中的作用。
在这项研究中,我们分析了88例初治MDS患者p21的表达情况和p73的甲基化情况。
我们发现与低危组或健康对照组相比,高危组MDS的p21基因的表达下降(P<0.05)。伴p73甲基化的患者P21表达低于非甲基化组(P<0.001)。此外,在MDS患者中p73和p21的表达呈显着正相关(r=0.436,P<0.001)。体外测定法进一步证实p73基因的甲基化对p21表达的影响。

无论是在单变量和多变量分析中,与p21基因表达正常的患者相比,p21低表达的患者更可能向急性髓细胞性白血病转化,并有着更低的总体生存率。我们的结果表明p21的表达可作为一种新的生物标志物来预测MDS患者的临床结果。

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