急性白血病死亡相关蛋白激酶基因启动子的甲基化

目的 研究死亡相关蛋白激酶(DAPK)基因启动子甲基化和基因表达在初治急性白血病患者中的临床意义.方法 采用MSP方法和RT-PCR方法分别检测60例急性髓系白血病患者、55例急性淋巴细胞白血病患者和17例正常人DAPK基因的甲基化状态及其mRNA的表达,统计学分析各组之间的表达差异.结果 急性淋巴细胞白血病组的DAPK甲基化阳性率(29.1％)高于急性髓细胞白血病组(5％)和正常组(0％)(P＜0.0l25),但甲基化与急性淋巴细胞白血病组患者临床特征无关(P＞0.05).DAPK基因mRNA的表达水平以正常组最高,急性髓细胞白血病组次之,急性淋巴细胞白血病组最低(P=0.000).急性淋巴细胞白血病组患者DAPK mRNA表达与其启动子甲基化呈显著负相关(P＜0.05).结论 DAPK基因启动子在初治急性淋巴细胞白血病患者中甲基化率高于初治急性髓细胞白血病患者和正常人,但与患者临床特征无关.急性淋巴细胞白血病患者DAPK基因表达水平低或不表达可能与其甲基化有关.

Promoter methylation and expression of death-associated protein kinase gene in acute leukemia

Objective To study the clinical implications of death-associated protein kinase (DAPK) promoter methylation and DAPK gene expression in untreated patients with acute leukemia.Methods Methylation-specific PCR and RT-PCR were employed to detect the DAPK gene methylation and mRNA expression in the bone marrow of 60 patients with acute myeloid leukemia (AML),55 patients with acute lymphocytic leukemia (ALL),and 17 normal subjects.Results The positivity rate of DAPK methylation was significantly higher in ALL patients (29.1％) than in AML patients group (5％) and normal subjects (0％) (P＜0.01).No correlation was found between DAPK gene methylafion and the clinical features in ALL patients (P＞0.05).DAPK mRNA expression level differed signiticantly among the 3 groups (P=0.000),and was the highest in normal subjects and the lowest in ALL patients.In ALL patients,the expression level of DAPK mRNA showed a significant inverse correlation with DAPK promoter methylation (P＜0.05).Conclusion The methylation rate of DAPK gene is higher in untreated ALL patients than in AML patients and normal subjects.DAPK gene methylation is not correlated with the clinical features of ALL patients but is probably related with the low gene expression level of DAPK in these patients.