Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Int J Lab Hematol. 2010 Feb;32(1 Pt 2):74-81. doi: 10.1111/j.1751-553X.2008.01131.x. Epub 2009 Jan 2.
Promoter hypermethylation plays an important role in the inactivation of cancer-related genes. This abnormality occurs early in leukemogenesis and seems to be associated with poor prognosis in myelodsplastic syndrome (MDS). The identification of more inactivated tumor suppressor genes contributing to the development of MDS may lead to further elucidation of the biology of this disease and help to identify novel targets for therapy. In this study, the methylation status of death-associated protein kinase 1 (DAPK1) gene promoter was analyzed by using methylation-specific polymerase chain reaction in bone marrow (BM) samples from 59 patients with different stages of MDS. The abnormal methylation of the DAPK1 gene was found in 37 of 59 (62.7%) MDS cases. The correlation was significant between the sex and the methylation status of DAPK1 promoter in MDS patients (R=0.332, P=0.010). Furthermore, methylation status of DAPK1 promoter was associated with the percentage of BM blasts (R=0.346, P=0.010) and International Prognosis Scoring System (IPSS) groups (R=0.278, P=0.034). The estimated 50% survival time of the methylated DAPK1 group and unmethylated group was 20 and 33 months, respectively. There was no significant difference between these two groups (chi2=0.652, P=0.419). Multivariate analysis identified the age older than 50 years, the Int-2/high-risk categories of IPSS and the advanced stage MDS (RAEB-1/RAEB-2) in WHO classification as negative prognostic factors (P<0.05). Aberrant methylation of DAPK1 gene promoter had no influence on the prognosis of MDS despite of its increasing occurrence during disease progression.
启动子异常甲基化在肿瘤相关基因失活中发挥重要作用。这种异常在白血病发生的早期就出现了，似乎与骨髓增生异常综合征（MDS）的不良预后有关。鉴定更多导致 MDS 发生的失活肿瘤抑制基因可能会进一步阐明该疾病的生物学特性，并有助于鉴定新的治疗靶点。在这项研究中，采用甲基化特异性聚合酶链反应分析了 59 例不同阶段 MDS 患者骨髓（BM）样本中死亡相关蛋白激酶 1（DAPK1）基因启动子的甲基化状态。在 59 例 MDS 病例中，有 37 例（62.7%）存在 DAPK1 基因异常甲基化。MDS 患者中 DAPK1 启动子的甲基化状态与性别之间存在显著相关性（R=0.332，P=0.010）。此外，DAPK1 启动子的甲基化状态与 BM 原始细胞的百分比（R=0.346，P=0.010）和国际预后评分系统（IPSS）分组（R=0.278，P=0.034）相关。甲基化 DAPK1 组和未甲基化组的估计 50%生存时间分别为 20 个月和 33 个月，两组之间无显著差异（chi2=0.652，P=0.419）。多因素分析表明，年龄大于 50 岁、IPSS 的 Int-2/高危分类和 MDS 的晚期（RAEB-1/RAEB-2）在 WHO 分类中是负预后因素（P<0.05）。尽管 DAPK1 基因启动子异常甲基化在疾病进展过程中发生率增加，但对 MDS 的预后没有影响。
