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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 investigate the methylation status of CDH13 gene promoter region in patients with acute myeloid leukemia (AML). Methods: Bone marrow cells from 76 patients with primary AML and 13 patients with AML before and after primary chemotherapy were selected as the experimental group. The bone marrow samples from 11 patients with IDA were used as the control group and 10 healthy controls Peripheral blood samples were taken as observation group. The pyrosequencing method was used to detect the promoter methylation level of CDH13 gene in all the subjects and the relationship between CDH13 gene promoter methylation status and the clinical features of AML patients. RESULTS: Of the 76 patients with primary untreated AML, 41 had CDH13 hypermethylation with a methylated positive rate of 53.9%. Thirteen cases of AML patients who were completely relieved after initial chemotherapy did not have hypermethylation of CDH13 gene. In the 13 cases, 8 cases of CDH13 gene hypermethylation, methylation positive rate was 61.5% and methylation average was 27.65% , The methylation level of CDH13 gene before treatment was significantly higher than that after treatment (t = 4.724, P <0.01). The positive rate of hypermethylation of CDH13 promoter between primary untreated AML and IDA specimens was statistically significant (53.9%: 9.1%, χ2 = 7.743, P = 0.008). The positive rate of CDH13 gene in M2 genotypes of primary untreated AML patients was significantly higher than that of other genotypes (P <0.05). There is no significant correlation between hypermethylation of CDH13 gene and the age and sex of AML patients and the existence of chromosome t (8,21) in M2 patients. CONCLUSION: Hypermethylation of CDH13 promoter region is prevalent in AML, which may be one of the molecular mechanisms that cause AML.