骨髓增生异常综合征患者p15启动子区域异常甲基化的临床研究

THE CLINICAL STUDY OF ABERRANT METHYLATION AND EXPRESSION OF p15 PROMOTER IN PATIENTS WITH MYELODYSPLASTIC SYNDROME

目的:探讨骨髓增生异常综合征(MDS)患者抑癌基因p15启动子区域异常甲基化的发生情况及其在发病机制中的作用。方法:收集41例初诊MDS患者及10例正常骨髓捐献者的骨髓,用甲基化特异性PCR(MSP)方法检测p15启动子CpG岛甲基化的发生情况,并分析p15基因启动子区域异常甲基化状态与MDS患者各项临床资料的关系。结果:在41例MDS患者中,有24例(58.5%)检测出p15启动子区域发生甲基化。对照组中无一例检测出p15启动子区域异常甲基化,两组比较差异有统计学意义(P<0.05)。其中RAEB-1、RAEB-2患者p15启动子区域异常甲基化的发生率明显高于RCUD、RARS和MDS-U患者(71.4%vs 12.5%,P=0.024)。按照MDS国际预后评分系统(IPSS)将患者分组发现,中高危组p15启动子区域异常甲基化发生率明显高于低危组(P=0.017)。染色体核型异常的MDS患者p15启动子区域异常甲基化发生率(9/10,90%)明显高于染色体核型正常的患者(6/16,37.5%)(P=0.014)。结论:MDS患者p15启动子区域异常甲基化与染色体畸变有关联,可能是MDS发病机制的重要因素之一,有望成为不良预后的判断指标。

Objective：To study the methylation status of p15 gene promoter of patients with myelodysplastic syndrome（MDS）and to explore its pathogenesis significance.Methods：Methylation of p15 promoter was detected in bone marrow cells of 41 MDS patients and 10 healthy controls by methylation-specific PCR（MSP）.We studied the relationship between abnormal p15 gene promoter region methylation status and the clinical data of patients with MDS.Results：p15 methylation was present in 24 MDS cases,at 58.5%（24/41）.No abnormal p15 gene promoter region methylation status was found in 10 healthy controls（P〈0.05）.The patients of RAEB1 and RAEB2exhibited a significantly higher frequency of p15 methylation than those of RCUD、RARS and MDS-U（71.4% vs 12.5%,P =0.024）.According to the MDS International Prognostic Scoring System（IPSS）,we found that p15 promoter methylation in the high-risk patient group was significantly higher than that in low-risk patient group（P =0.017）.The incidence of p15 promoter regions methylation in patients with chromosome karyotype abnormal was（90%,9/10）significantly higher than in those with normal chromosome karyotype（37.5%,6/16）（P =0.014）.Conclusion：The aberrant methylation status of p15 gene promoter in patients with myelodysplastic syndrome was correlated with chromosome aberration.And it could be one of the important indicators for prognosis.