摘要
目的:研究DKK-3和WIF-1在急性髓系白血病(AML)患者中的启动子甲基化状态和mRNA表达情况及其临床意义。方法:用甲基化特异性聚合酶链式反应(MSP)检测56例AML患者骨髓标本和20例缺铁性贫血患者(对照组)骨髓标本中DKK-3和WIF-1启动子甲基化状态;用实时定量PCR检测上述标本中β-catenin、DKK-3和WIF-1mRNA表达情况,并分析其与临床资料及生存时间的关系。结果:AML组中DKK-3和WIF-1启动子甲基化率明显高于对照组(χ2=15.330,P<0.001;χ2=17.371,P<0.001),且与性别、年龄、临床分型无相关性。DKK-3和WIF-1 mRNA相对表达量在AML患者中依次为0.840±0.320和0.792±0.313,明显低于对照组的1.134±0.392和1.047±0.334(t=3.415,P=0.000;t=3.070,P=0.003)。AML患者骨髓标本β-catenin的mRNA相对表达量为0.756±0.304,高于对照组骨髓标本表达量0.342±0.105(t=5.943,P=0.001),且AML骨髓标本中DKK-3和WIF-1 mRNA相对表达量和β-catenin相对表达量呈均呈负相关性(r=-0.543;r=-0.562)。KaplanMeier生存曲线分析显示,DKK-3甲基化阳性组AML患者总体生存时间短于阴性组患者(χ2=3.957,P=0.042),而WIF-1甲基化阳性组AML患者总体生存时间亦短于阴性组患者(χ~2=4.520,P=0.029)。结论:AML患者中Wnt/β-catenin信号通路存在有异常激活,DKK-3和WIF-1启动子甲基化可能参与了Wnt通路激活及AML的发病过程并影响其总体预后。
Objective： To analyze the promoter methylation status,mRNA expression and clinical significance of DKK-3 and WIF-1 genes in patients with acute myeloid leukemia（AML）. Methods： Methylation specific polymerase chain reaction（MS-PCR） mothod was carried out to detect DKK-3 and WIF-1 gene promoter methylation status in bone marrow specimen from 56 patients with AML and 20 patients with iron deficiency anaemia（IDA） as control; then the realtime quantitative reverse transcription polymerase chain reaction（RT-PCR） was used to detect mRNA expression of DKK-3,WIF-1 gene and β-catenin in the above-mentioned specinens,and their relationship with the clinical features and survival time was analyzed. Results： The promoter methylation rate of DKK-3 and WIF-1 gene in AML patients were significantly higher than that in control group（χ2 = 15. 330,P 0. 001; χ2 = 17. 371,P 0. 001）. There was no relationship between DKK-3 and WIF-1 gene promoter methylation rate and AML patient＇s sex,age,clinical typing. The relative expression of DKK-3 and WIF-1 gene mRNA in AML group were 0. 840 ± 0. 320 and 0. 792 ± 0. 313,which were lower than those in control group（1. 134 ± 0. 392 and 1. 047 ± 0. 334） respectively,the difference was statistically significant（t = 3. 415,P = 0. 000; t = 3. 070,P = 0. 003）. The relative expression of β-catenin mRNA in AML bone marrow specimens in AML group was 0. 756 ± 0. 304,which was higher than that in control group（0. 342 ± 0. 105）,the difference was statistically significant（t = 5. 943,P = 0. 001）. The expression of DKK-3 and WIF-1 gene mRNA negatively correlated with β-catenin mRNA（r =-0. 543; r =-0. 562）. Kaplan Meier survival curve analysis showed that overall survival time in AML patients with DKK-3 gene methylation was shorter than that in the AML patients with DKK-3 gene unmethylation（χ2 = 3. 957,P = 0. 042）. Futhermore,the orerall survival time in AML patients with WIF-1 genemethylation was also shorter than that in AML patients with WIF-1
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2017年第5期1314-1320,共7页
Journal of Experimental Hematology
