Wang Yu-chun, DU Xin, Geng Su-xia, Li Yue-ying, Weng Jian-yu, Lu Ze-sheng, Zhong Li-ye, Deng Cheng-xin, Lai Pei-long, Huang Xin
Department of Hematology, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Zhonghua Xue Ye Xue Za Zhi. 2011 Apr;32(4):254-8.
To analyze the promoter methylation levels of p15, CDH1, DAPK and HICI genes of patients with myelodysplastic syndrome (MDS) and explore the relationship between the level of methylation and clinical features.
DNA methylation levels of p15, CDH1, DAPK and HICI in peripheral blood (PB) or bone marrow (BM) samples from 52 MDS patients were detected by real-time quantitative PCR. The correlation of the methylation level with clinical features and hematological findings was analyzed. 38 de novo AML patients and 46 normal individuals served as controls.
The methylation levels of p15, CDH1, DAPK and HICI were 16.23 ± 21.69, 6.59 ± 9.39, 0.14 ± 0.11 and 7.81 ± 9.70 in BM, and 14.96 ± 20.16, 6.00 ± 9.26, 0.12 ± 0.14 and 6.74 ± 9.72 in PB, respectively from 18 MDS patients, and the difference between BM and PB was not statistically significant (P > 0.05). The methylation levels of p15 (14.70 ± 18.17) and CDH1 (6.61 ± 8.79) genes in high risk (RAEBI/II) MDS were significantly higher than in low risk (RCMD/RARS/5q-, p15: 1.99 ± 1.59, CDH1: 1.23 ± 1.14 and RCMD, p15: 3.02 ± 3.42, CDH1:1.53 ± 2.06) MDS or control (p15: 1.69 ± 1.82, CDH1: 1.01 ± 1.12) (P < 0.05). The methylation levels of DAPK gene had no difference among subtypes of MDS, and that of HIC1 gene only differed between RAEB I/II (9.16 ± 11.95) and control (2.49 ± 2.26) (P = 0.042). The difference of methylation levels of p15, CDH1, DAPK and HICI in BM was statistically significant among subtypes of MDS (P = 0.001, 0.003, 0.039, 0.023, respectively). And so did of p15 and DAPK in PB (P = 0.013, 0.006, respectively). The methylation level of p15 and CDH1 was significantly correlated with IPSS classification and blasts percentage in BM.
p15 and CDH1 genes are special hypermethylation genes in MDS. Methylation level of HIC1 gene showed an upward tendency from low risk to high risk MDS.
分析骨髓增生异常综合征（MDS）患者p15、CDH1、DAPK和HICI基因的启动子甲基化水平，探讨甲基化水平与临床特征之间的关系。
采用实时定量PCR检测52例MDS患者外周血（PB）或骨髓（BM）样本中p15、CDH1、DAPK和HICI的DNA甲基化水平。分析甲基化水平与临床特征及血液学检查结果的相关性。38例初发急性髓系白血病（AML）患者和46例正常个体作为对照。
18例MDS患者BM中p15、CDH1、DAPK和HICI的甲基化水平分别为16.23±21.69、6.59±9.39、0.14±0.11和7.81±9.70，PB中分别为14.96±20.16、6.00±9.26、0.12±0.14和6.74±9.72，BM与PB之间差异无统计学意义（P>0.05）。高危（RAEB I/II）MDS患者p15（14.70±18.17）和CDH1（6.61±8.79）基因的甲基化水平显著高于低危（RCMD/RARS/5q-，p15：1.99±1.59，CDH1：1.23±1.14以及RCMD，p15：3.02±3.42，CDH1：1.53±2.06）MDS或对照（p15：1.69±1.82，CDH1：1.01±1.12）（P<0.05）。DAPK基因的甲基化水平在MDS各亚型间无差异，HIC1基因仅在RAEB I/II（9.16±11.95）与对照（2.49±2.26）之间存在差异（P=0.042）。MDS各亚型间BM中p15、CDH1、DAPK和HICI甲基化水平差异有统计学意义（分别为P=0.001、0.003、0.039、0.023）。PB中p15和DAPK也是如此（分别为P=0.013、0.006）。p15和CDH1的甲基化水平与IPSS分类及BM中的原始细胞百分比显著相关。
p15和CDH1基因是MDS中特殊的高甲基化基因。HIC1基因的甲基化水平从低危MDS到高危MDS呈上升趋势。
