EZH2在急性髓系白血病病程中的表达和对预后判断的意义研究

Research progress and prognostic significance of EZH2 in acute myeloid leukemia

目的：探讨DNA甲基转移酶（DNA methyltransferase,DNMT1）与EZH2在急性髓系白血病（acute myeloid leukemia,AML）中的表达及其相关性。方法：采用荧光定量PCR（fluorescence quantitative PCR,FQ-PCR）检测大连医科大学附属第二医院2014年1月至2015年1月50例初治AML患者骨髓细胞中DNMT1与EZH2 m RNA的表达水平,分析DNMT1表达水平与临床特征和预后的关系以及与EZH2的相关性。结果：50例AML患者骨髓细胞中DNMT1 m RNA的表达显著高于30例正常供者（2.72±0.73 vs.0.89±0.27,P〈0.01）;EZH2的表达水平也显著高于正常供者（4.39±1.06 vs.1.87±0.33,P〈0.01）;EZH2与DNMT1的表达水平呈显著正相关（r=0.51,P=0.002）;DNMT1表达水平与外周血幼稚细胞比例≥60%（P〈0.05）、WBC≥50×109/L（P〈0.05）呈显著相关;DNMT1高表达组患者中位生存时间15个月（95%CI为9~19个月）,显著低于DNMT1低表达组患者的32个月（95%CI为27~40个月,P=0.006）。结论：DNMT1和EZH2在AML患者中均高表达,两者表达水平呈正相关,DNMT1与AML患者预后不良相关。

Objective： To investigate the relationship between DNA methyltransferase （DNMT1） and EZH2 gene expression levels and their clinical significance in patients with acute myeloid leukemia （AML）. Methods： The mRNA expression levels of DNMT2 and EZH2 in 50 AML cases and 30 healthy controls were quantified through real-time PCR. The relationship among DNA methyltransferase （DNMT]） and EZH2, clinicopathological factors, and prognosis was analyzed. Results： The mRNA expression of DNMT1 in the AML cases （2.72±0.73） was significantly higher than that in the healthy controls （0.89±0.27） （P〈0.02）. The mRNA expression of EZH2 in the AML cases （4.39±1.06） was also significantly higher than that in the healthy controls （1.87±0.33） （P〈0.02）. The expression of DNMT1 was positively associated with that of EZH2 （r=0.51, P=0.002）. The expression of DNMT2 was also associated with PB% and WBC ≥50x209/L （P〈 0.05）. The overall survival of the group with a high-mRNA-expressing DNMT1 was 15 months （95% C1=9-19 months）. This period was significantly shorter than that of the group with Iow-mRNA-expressing DNMT1 （32 months, 95% C1=27-40 months; P=0.006）. Conclusion： DNMT/and EZH2 expression levels were downregulated. These levels were associated with poor AML prognosis. The expression of DNMT1 was also positively associated with that of EZH2.