Objective: To investigate the methylation status of CHD5 gene promoter in bone marrow from acute myeloid leukemia (AML) patients, and the underlying mechanism for initiating the pathogenesis of AML via p19Arf/p53/p21Cip1 pathway.
Methods: Methylation status of the CHD5 gene promoter was detected by using methylation-specific polymerase chain reaction (MSPCR) in bone marrow from AML patients, and the iron-deficiency anemia (IDA) samples were served as control. The expression of CHD5, p19Arf, p53 and p21Cip1 was determined by real-time quantitative reverse transcriptase PCR and Western blot.
Results: The methylation of CHD5 gene in bone marrow from AML patients increased significantly (39.06%) as compared with control group (6.67%). The methylation of CHD5 gene significantly correlated with chromosome karyotype differentiation (P＜0.01), but did not correlate with the patient's sex, age and clinical classification (P＞0.05). The mRNA expression of CHD5 gene in AML decreased, compared with control group, the mRNA and protein expression of p19Arf, p53 and p21Cip1 in AML with CHD5 methylation promoter decreased.
Conclusion: The hypermeltylation of CHD5 gene promoter in AML patients can lead to decrease of CHD5, p19Arf, p53 and p21Cip1 expression levels which may reduce the inhibitory effect on proliferation of leukemia cells through the regulation of p19Arf, p53 and p21Cip1 pathway, thus promotes the occurence of AML.
题目: CHD5基因启动子甲基化调控p19Arf/p53/p21Cip1信号通路促进急性髓系白血病发病的研究.
目的: 探讨急性髓系白血病患者（AML）骨髓中CHD5基因甲基启动子甲基化状态及其调控p19Arf/p53/p21Cip1信号通路促进AML发病的机制.
方法: 采用MSP检测AML组及对照组CHD5基因甲基化状态，应用实时定量RT-PCR和Western blot检测CHD5、p19Arf、p53及p21Cip1的表达水平.
结果: AML患者骨髓中CHD5基因甲基化率（39.06%）较对照组（6.67%）明显增高（P＜0.05）；CHD5基因甲基化与AML不同染色体核型相关（P=0.009），但与性别、年龄及临床分型无显著相关（P＞0.05）；AML患者CHD5相对表达水平明显低于对照组（P＜0.05）；存在CHD5甲基化AML患者p19Arf、p53及p21Cip1基因和蛋白表达水平较对照组降低.
结论: AML患者CHD5基因启动子的高甲基化可导致CHD5、p19Arf、p53和p21Cip1表达水平下降，从而可能通过调控p19Arf/p53/p21Cip1途径减弱对白血病细胞增殖抑制作用，促进AML的发生.