CAJ | 학술논문

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.
목적 료해골수증생이상종합정(MDS)환자WNT/β-catenin신호전도통로중길항기인Dickkopf-3(Dkk3)적갑기화상태,초보탐색기갑기화상태여MDS발생급질병진전적관계.방법 응용갑기화특이성PCR(MSP)법대43례MDS환자적골수혹외주혈Dkk3기인계동자구갑기화상황진행검측,병이70례문진보통환자적외주혈검측결과작위대조,동시대환자진행수방.결과 43례MDS환자중검출7례(16.3％)Dkk3갑기화,기중5례(11.6％)위반갑기화상태,2례(4.7％)위완전갑기화상태,70례정상대조중1례(1.4％)위Dkk3갑기화,조간DKK3갑기화솔차이유통계학의의(x2=8.93,P=0.005).7례Dkk3갑기화적양본중,2례래자골수,5례래자외주혈,기중난치성빈혈(RA)2례,난치성세포감소반다계이상(RCMD)1례,난치성빈혈반원시세포증다(RAEB)4례.단인소분석시불동성별、염색체핵형、양본래원(골수/외주혈)、위험도(WHO분류적예후평분계통≤2분급＞2분)급노년조여비노년조간갑기화솔차이균무통계학의의(균P＞0.05).재35례장기수방환자중,9례환자전화위급성수계백혈병(AML)(6례DKK3갑기화자중3례,29례DKK3비갑기화자중6례),질병진전조여은정조간갑기화솔차이무통계학의의(P＞0.05);사망12례중3례위Dkk3갑기화양성,단갑기화여비갑기화조간생존솔차이무통계학의의(P＞0.05).결론 MDS환자중Dkk3기인존재교고적갑기화수식,저가능시MDS발병적분자궤제지일.본조환자례수교소,상미발현갑기화여림상예후간적상관성.
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.