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

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

机构信息

Dept of Hematology, Shanghai Sixth People's Hospital affiliated to Shanghai Jiaotong University, 200233 Shanghai, China;

出版信息

Am J Clin Pathol. 2013 Dec;140(6):819-27. doi: 10.1309/AJCPZ5E6IWPWSZXE.

DOI:10.1309/AJCPZ5E6IWPWSZXE

PMID:24225749

Abstract

OBJECTIVES

p21 Can both promote and inhibit tumorigenic processes. We explored the role of p21 in myelodysplastic syndrome (MDS).

METHODS

In this study, we analyzed p21 expression and p73 methylation in 88 patients with de novo MDS.

RESULTS

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.

CONCLUSIONS

Our results suggest p21 expression may serve as a new biomarker to predict clinical outcome in patients with MDS.

摘要

目的

p21 既能促进又能抑制肿瘤发生过程。我们探讨了 p21 在骨髓增生异常综合征（MDS）中的作用。

方法

本研究分析了 88 例初发 MDS 患者的 p21 表达和 p73 甲基化情况。

结果

与低危组或健康对照组相比，高危 MDS 患者 p21 基因表达降低（P<.05）。p73 甲基化患者的 p21 表达低于未甲基化组（P<.001）。此外，MDS 中 p73 和 p21 的表达呈显著正相关（r=0.436，P<.001）。体外实验进一步证实了 p73 甲基化在 p21 表达中的作用。与 p21 表达水平正常的患者相比，p21 表达水平较低的患者在单变量和多变量分析中均有更高的向急性髓系白血病转化的发生率和更低的总生存率。