急性髓系白血病CDH13基因启动子甲基化的定量研究

Quantitive analysis of promoter methylation of CDH13 gene in patients with acute myeloid leukemia

目的:探讨急性髓系白血病(AML)患者抑癌基因CDH13基因启动子区域的甲基化情况。方法:选取76例原发初治AML患者的骨髓细胞及其中13例AML患者首次化疗前后的骨髓细胞作为实验组,11例缺铁性贫血(IDA)患者的骨髓标本作为对照组,10例健康者外周血标本作为观察组。应用焦磷酸测序方法检测所有入选对象CDH13基因启动子甲基化水平,并初步探讨其与AML患者临床特征的关系。结果:76例原发初治AML患者中41例CDH13基因高甲基化,甲基化阳性率为53.9%。13例首次化疗后完全缓解的AML患者均未有CDH13基因高甲基化,而这13例标本初诊时有8例CDH13基因高甲基化,甲基化阳性率为61.5%,甲基化平均值为27.65%,治疗前CDH13基因甲基化水平显著高于治疗后(t=4.724,P<0.01)。原发初治AML与IDA标本CDH13基因启动子高甲基化阳性率差异有统计学意义(53.9%∶9.1%,χ2=7.743,P=0.008)。CDH13基因在原发初治AML患者M2分型中高甲基化阳性率,明显高于其他各型(P<0.05)。CDH13基因的高甲基化与AML患者的年龄、性别及M2患者是否存在染色体t(8,21)无明显相关性。结论:CDH13基因启动子区域高甲基化在AML中普遍存在,其可能是引起AML的分子机制之一。

Objective：To explore the clinical significance of promoter methylation of CDH13 gene in patients with acute myeloid leukemia （AML）. Method：The promoter methylation of CDH13 gene were detected by pyrose- quencing method in bone marrow of 76 cases with primary de novo AML,13 pairs of AML in complete remission （CR） before and after the first chemotherapy,11 cases of iron deficiency anemia （IDA） and peripheral blood sam ples of 10 cases of healthy individuals. Result：Promoter hypermethylation of CDH13 were detected in 41 cases （53. 9~） among 76 cases with primary de novo AML,whiie only one case （9.1%） among 11 cases with IDA （P^0. 01）. The 13 pairs were detected positive in 8 cases before treated while none after the first chemotherapy with CR （P^0.01）. The promoter hypermethylation of CDH13 was more common in de novo AML of subtype Me than those in other FAB subtypes （P%0.05）. The promoter hypermethylation of CDH13 was unrelated with age,gen- der of primary de novo AML patients and presence of the chromosome abnormality t（8,21） in de novo AML of subtype M2. Conclusion：The abnormal hypermethylation in the promoter region of the CDH13 gene is a common feature in AMl.,which may be one of the molecular mechanisms of the pathogenesis of AML.