Department of Hematology, Huashan Hospital of Fudan University, Shanghai, P.R. China.
Tohoku J Exp Med. 2012 Jun;227(2):119-28. doi: 10.1620/tjem.227.119.
Myelodysplastic syndrome (MDS), characterized by the decreased production of blood cells, often progresses to acute myeloid leukemia (AML), a sign of poor prognosis of MDS. In AML, the Wnt/β-catenin pathway is aberrantly activated, suggesting that the increased pathway activity may be correlated with the development and prognosis of MDS. SOX7 protein, encoded by the sex-determining region Y-box 7 (SOX7) gene, inhibits the activity of the Wnt/β-catenin pathway. Because the DNA methylation can regulate the transcription of SOX7 gene, we used the methylation-specific PCR to investigate the methylation status of the CpG island in MDS patients to determine the potential correlation of the SOX7 methylation with the development and prognosis of MDS. We found that the CpG island of the SOX7 gene was methylated in 58.1% (97/167) of MDS patients, but not in any healthy control. Furthermore, the percentage of patients with the methylated CpG island of the SOX7 gene was significantly higher in patients at advanced stages of MDS than in the patients at early stages. The increased percentages of this SOX7 methylation were also correlated with age, marrow blast levels, and International Prognostic Scoring System (IPSS) risk. After prognostic analysis, we found that patients with the methylated CpG island of the SOX7 gene had shorter overall survival and cumulative survival than patients with unmethylated CpG island. Our findings suggest that the methylation of the CpG island of the SOX7 gene can be used as a predictive factor for the development and prognosis of MDS patients.
骨髓增生异常综合征（MDS）的特征是血细胞生成减少，常进展为急性髓系白血病（AML），这是 MDS 预后不良的标志。在 AML 中，Wnt/β-catenin 途径异常激活，表明该途径活性的增加可能与 MDS 的发生和预后相关。SOX7 蛋白由性别决定区 Y 框 7（SOX7）基因编码，可抑制 Wnt/β-catenin 途径的活性。由于 DNA 甲基化可以调节 SOX7 基因的转录，我们使用甲基化特异性 PCR 来研究 MDS 患者中 CpG 岛的甲基化状态，以确定 SOX7 甲基化与 MDS 的发生和预后的潜在相关性。我们发现，SOX7 基因的 CpG 岛在 58.1%（97/167）的 MDS 患者中发生甲基化，但在任何健康对照中均未发生。此外，SOX7 基因 CpG 岛甲基化的患者比例在 MDS 晚期患者中明显高于早期患者。这种 SOX7 甲基化的增加百分比也与年龄、骨髓原始细胞水平和国际预后评分系统（IPSS）风险相关。预后分析后，我们发现 SOX7 基因 CpG 岛甲基化的患者总生存期和累积生存率均短于 CpG 岛未甲基化的患者。我们的研究结果表明，SOX7 基因 CpG 岛的甲基化可用作预测 MDS 患者发生和预后的标志物。
