骨髓增生异常综合征患者Dickkopf-3基因启动子区甲基化状态研究  

Methylation status in the promoter region of Dickkopf-3 gene in patients with myelodysplastic syndromes

作　　者：范芸[1] 史晓红[2] 宁尚勇[1] 李江涛[1] 程玮[1] 常乃柏[1] 杨泽[2] 

机构地区：[1]卫生部北京医院血液科,100730 [2]卫生部北京老年医学研究所医学遗传室

出　　处：《白血病．淋巴瘤》2014年第9期534-537,共4页Journal of Leukemia & Lymphoma

摘　　要：目的 了解骨髓增生异常综合征（MDS）患者WNT/β-catenin信号转导通路中拮抗基因Dickkopf-3（Dkk3）的甲基化状态,初步探索其甲基化状态与MDS发生及疾病进展的关系.方法 应用甲基化特异性PCR（MSP）法对43例MDS患者的骨髓或外周血Dkk3基因启动子区甲基化状况进行检测,并以70例门诊普通患者的外周血检测结果作为对照,同时对患者进行随访.结果 43例MDS患者中检出7例（16.3％）Dkk3甲基化,其中5例（11.6％）为半甲基化状态,2例（4.7％）为完全甲基化状态,70例正常对照中1例（1.4％）为Dkk3甲基化,组间DKK3甲基化率差异有统计学意义（x2=8.93,P=0.005）.7例Dkk3甲基化的样本中,2例来自骨髓,5例来自外周血,其中难治性贫血（RA）2例,难治性细胞减少伴多系异常（RCMD）1例,难治性贫血伴原始细胞增多（RAEB）4例.单因素分析示不同性别、染色体核型、样本来源（骨髓/外周血）、危险度（WHO分类的预后评分系统≤2分及＞2分）及老年组与非老年组间甲基化率差异均无统计学意义（均P＞0.05）.在35例长期随访患者中,9例患者转化为急性髓系白血病（AML）（6例DKK3甲基化者中3例,29例DKK3非甲基化者中6例）,疾病进展组与稳定组间甲基化率差异无统计学意义（P＞0.05）;死亡12例中3例为Dkk3甲基化阳性,但甲基化与非甲基化组间生存率差异无统计学意义（P＞0.05）.结论 MDS患者中Dkk3基因存在较高的甲基化修饰,这可能是MDS发病的分子机制之一.本组患者例数较少,尚未发现甲基化与临床预后间的相关性.Objective To investigate the methylation status in the promoter region of Dickkopf-3 （Dkk3） gene in patients with myelodysplastic syndromes （MDS）,and to initially explore the relationship between the methylation of this gene and survival time.Methods Methylation-specific PCR （MSP） was applied to measure the promoter methylation of Dkk3 gene in 43 bone marrow or peripheral blood samples of MDS patients.As controls,70 normal peripheral blood samples from general outpatients were examined.Results In 43 patients with MDS,7 patients （16.3 ％） showed Dkk3 gene methylation.And 5 of them were semi-methylation status,2 of them were exhaustive methylation status.In 70 controls,1 showed Dkk3 gene semi-methylation.The frequency of methylation in MDS patients was significantly higher than that of controls （x2 =8.93,P =0.005）.In the Dkk3 methylation group,2/7 were from bone marrow and 5/7 were from peripheral blood.Meanwhile,2 patients were RA,1 patient was RCMD,4 patients were RAEB.There was no significant difference between the different sample source （bone marrow or peripheral blood） for the results of the methylation status （x2 =0.051,P =0.821）.Either between the different sex,age,type,chromosome and WPSS score （P ＞ 0.05）.The progress of disease didn＇t influence the methylation frequency （P ＞ 0.05）.The smvival analysis showed no relationship between the methylation of this gene and smvival time.Conclusions In this MDS group,there is high level of methyl-modification in Dkk3 gene.The methylation of Dkk3 might be one of the molecular mechanisms that contribute to the progress of patients with MDS.The peripheral blood sample maybe a better substitute in detective of Dkk3 with MDS.

关 键 词：骨髓增生异常综合征 Dickkopf-3基因 甲基化 外周血 

分 类 号：R551.3[医药卫生—血液循环系统疾病]