慢性髓细胞白血病患者PRAME基因启动子甲基化改变

Alteration of methylation status of PRAME gene promoter in patients with chronic myeloid leukemia

目的:慢性髓系白血病(chronic myeloid leukemia,CML)患者中黑色素瘤优先表达抗原(PRAME)基因启动子区域的甲基化改变其及其临床相关性。方法:应用实时定量甲基化特异性PCR(real-time quantitative methylation-specific PCR,RQ-MSP)技术对55例CML患者及20例对照组骨髓单个核细胞标本的PRAME基因启动子甲基化状态进行检测。结果:28/55例(51%)CML患者出现PRAME启动子低甲基化改变,而20例对照未显示低甲基化,两组差异有显著统计学意义(P<0.001)。PRAME低甲基化与患者血液学相关参数及染色体分组均无相关性。PRAME启动子低甲基化频率随疾病进展而降低,在慢性期、加速期及急变期中分别为48%(22/46)、33%(1/3)及17%(1/6)。结论:PRAME基因低甲基化可能是参与CML发生的早期分子事件之一。

Objective To analyze the methylation status of PRAME gene promoter and its correlations with clinical features in patients with chronic myeloid leukemia （CML）. Methods Real-time quantitative methylation-specific PCR （RQ-MSP） assay was used to detect the methylation level of PRAME promoter in bone marrow samples from patients with CML （n = 55） and controls （n = 20）. Results Hypomethylation of PRAME promoter was detected in 28 （51%） CML patients, but was not found in all 20 controls （P 〈 0.001）. PRAME hypomethylation was not correlated with blood parameters or chromosomal abnormalities （P〉 0.05）. The frequencies of PRAME promoter hypomethylation were decreased with the disease progression, and were 48% （22/46）, 33% （1/3） and 17% （1/6） in chronic phase （CP）, accelerated phase （AP） and blast crisis （BC）, respectively. Conclusion Hypomethylation of PRAME promoter may be one of the molecular events involved in the disease progression of CML.