急性髓系白血病儿童DKK3基因启动子高甲基化的临床价值

Clinical value of the promoter hypermethylation of DKK3 gene in children with acute myeloid leukemia

目的检测急性髓系白血病(AML)患儿骨髓DKK3基因启动子甲基化情况并研究其临床意义。方法选择急性髓系白血病患儿(AML组)80例和血液系统良性疾病患儿(CON组)40例为研究对象,采用甲基化特异性PCR检测两组患儿骨髓DKK3基因启动子甲基化并比较其差异,分析AML组患儿不同临床病理因素中DKK3基因启动子甲基化的差异,对比DKK3基因启动子甲基化与未甲基化患儿3年生存率及总生存时间的差异。检测髓系白血病细胞株DKK3基因启动子甲基化状态。结果 AML组患儿骨髓DKK3基因启动子甲基化率高于CON组(P﹤0.05);AML组患儿骨髓DKK3基因启动子甲基化在性别、年龄、初诊发热、外周血白细胞(WBC)、外周血红细胞(RBC)、外周血血小板(PLT)和FAB分型方面比较,差异均无统计学意义(P﹥0.05),在骨髓原始细胞比例、核型类型和诱导化疗疗效方面比较,差异均有统计学意义(P﹤0.05);随访3年,AML组DKK3基因启动子甲基化患儿的生存率和生存时间均较DKK3基因启动子未甲基化患儿低(P﹤0.05);HL-60、KG-1和K562白血病细胞株DKK3基因启动子均处于甲基化状态。结论急性髓系白血病患儿骨髓DKK3基因启动子处于高甲基化状态,在病情及预后评估中具有一定价值。

Objective To study the clinical value of promoter hypermethylation of the DKK3 gene in children with acute myeloid leukemia （AML）. Method 80 children with AML and 40 cases of benign hematologic disorders were in-cluded in the study as study group and control group, respectively. Methylation-specific PCR was used to detect the pro-moter methylation of DKK3 gene in both groups, and the promoter methylation of DKK3 gene in study group with varied clinicopathological factors were compared, besides, the 3-year survival rate and overall survival between children with and without promoter methylation of the DKK3 gene were compared. The methylation of DKK3 gene promoter in leuke-mia cell line HL-60, KG-1 and K562 were detected. Result The rate of promoter methylation of the DKK3 gene was sig-nificantly higher in study group than in control group （P〈0.05）;In study group, the promoter methylation status was simi-lar in regard of gender, age, newly diagnosed fever, peripheral WBC, peripheral RBC, peripheral PLT and FAB typing （all P〉0.05）, while significant differences were observed in respect of bone marrow original cell proportion, karyotype classi-fication and efficacy of induction chemotherapy （all P〈0.05）;After 3-year follow-up, survival rate and survival time in study group were all significantly worse than the children without promoter methylation of DKK3 gene （P〈0.05）;Promot-er methylation was observed in the DKK3 gene of leukemia cell line HL-60, KG-1 and K562. Conclusion The DKK3 gene promoter is hypermethylated in children with acute myeloid leukemia, which is of clinical value in the evaluation of disease condition and prognosis.