中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2012年
10期
847-851
,共5页
赵佑山%杨瑞%顾树程%郭娟%张曦%吴凌云%李晓%常春康
趙祐山%楊瑞%顧樹程%郭娟%張晞%吳凌雲%李曉%常春康
조우산%양서%고수정%곽연%장희%오릉운%리효%상춘강
DNA甲基化%基因,p73%骨髓增生异常综合征%预后
DNA甲基化%基因,p73%骨髓增生異常綜閤徵%預後
DNA갑기화%기인,p73%골수증생이상종합정%예후
DNA methylation%Gene%p73%Myelodysplastic syndrome%Prognosis
目的 探讨骨髓增生异常综合征(MDS)患者抑癌基因p73启动子区域甲基化情况及其在预后中的意义.方法 收集135例初诊MDS患者及13名正常志愿者骨髓细胞,用甲基化特异性PCR (MS-PCR)方法检测p73基因启动子CpG岛甲基化发生情况,并利用亚硫酸盐测序法验证MS-PCR结果；荧光定量PCR法检测p73 mRNA表达情况；利用地西他滨处理MDS患者原代细胞,观察p73基因去甲基化及p73 mRNA表达情况；结合临床资料分析p73基因异常高甲基化在MDS中的作用.结果 37.0％的MDS患者p73基因启动子呈高甲基化状态,而且高危组MDS患者(RAEB-1、RAEB-2)甲基化发生率明显高于低危组(58.8％对29.7％,P=0.002)；甲基化组患者p73 mRNA表达水平显著低于非甲基化组(P=0.032)；用地西他滨处理后,可见MDS原代细胞p73去甲基化,且p73mRNA表达水平增高；p73高甲基化患者无白血病生存时间(DFS)及总体生存时间(OS)低于p73非甲基化患者(P值均＜0.01).在COX模型中,p73基因甲基化状况和骨髓原始细胞水平为影响患者DFS及OS的独立预后因素.结论 p73基因启动子高甲基化在MDS患者中较常见,且提示预后不良,可能为地西他滨治疗的靶点.
目的 探討骨髓增生異常綜閤徵(MDS)患者抑癌基因p73啟動子區域甲基化情況及其在預後中的意義.方法 收集135例初診MDS患者及13名正常誌願者骨髓細胞,用甲基化特異性PCR (MS-PCR)方法檢測p73基因啟動子CpG島甲基化髮生情況,併利用亞硫痠鹽測序法驗證MS-PCR結果；熒光定量PCR法檢測p73 mRNA錶達情況；利用地西他濱處理MDS患者原代細胞,觀察p73基因去甲基化及p73 mRNA錶達情況；結閤臨床資料分析p73基因異常高甲基化在MDS中的作用.結果 37.0％的MDS患者p73基因啟動子呈高甲基化狀態,而且高危組MDS患者(RAEB-1、RAEB-2)甲基化髮生率明顯高于低危組(58.8％對29.7％,P=0.002)；甲基化組患者p73 mRNA錶達水平顯著低于非甲基化組(P=0.032)；用地西他濱處理後,可見MDS原代細胞p73去甲基化,且p73mRNA錶達水平增高；p73高甲基化患者無白血病生存時間(DFS)及總體生存時間(OS)低于p73非甲基化患者(P值均＜0.01).在COX模型中,p73基因甲基化狀況和骨髓原始細胞水平為影響患者DFS及OS的獨立預後因素.結論 p73基因啟動子高甲基化在MDS患者中較常見,且提示預後不良,可能為地西他濱治療的靶點.
목적 탐토골수증생이상종합정(MDS)환자억암기인p73계동자구역갑기화정황급기재예후중적의의.방법 수집135례초진MDS환자급13명정상지원자골수세포,용갑기화특이성PCR (MS-PCR)방법검측p73기인계동자CpG도갑기화발생정황,병이용아류산염측서법험증MS-PCR결과；형광정량PCR법검측p73 mRNA표체정황；이용지서타빈처리MDS환자원대세포,관찰p73기인거갑기화급p73 mRNA표체정황；결합림상자료분석p73기인이상고갑기화재MDS중적작용.결과 37.0％적MDS환자p73기인계동자정고갑기화상태,이차고위조MDS환자(RAEB-1、RAEB-2)갑기화발생솔명현고우저위조(58.8％대29.7％,P=0.002)；갑기화조환자p73 mRNA표체수평현저저우비갑기화조(P=0.032)；용지서타빈처리후,가견MDS원대세포p73거갑기화,차p73mRNA표체수평증고；p73고갑기화환자무백혈병생존시간(DFS)급총체생존시간(OS)저우p73비갑기화환자(P치균＜0.01).재COX모형중,p73기인갑기화상황화골수원시세포수평위영향환자DFS급OS적독립예후인소.결론 p73기인계동자고갑기화재MDS환자중교상견,차제시예후불량,가능위지서타빈치료적파점.
Objective To study the methylation status of p73 gene promoter in patients with myelodysplastic syndrome (MDS) and explore its significance with clinical prognosis.Methods Methylation of p73 promoter was detected in bone marrow cells from 135 MDS patients and 13 healthy controls by methylation-specific PCR (MSP).The results of MSP were confirmed by bisulfite sequencing.The expression of p73 mRNA was detected by real-time quantitative PCR.Primary bone marrow cells from MDS patients were treated with decitabine,the changes of p73 methylation status and p73 mRNA expression were measured.The role of p73 methylation in the prognosis of MDS and the correlated clinical data were explored.Results p73 hypermethylation was present in 37.04％ of MDS cases and patients with high risk MDS (RAEB-1 and RAEB-2)exhibited a significantly higher frequency of p73 methylation than that of low risk MDS (58.8％ vs 29.7％,P =0.002).The expression of p73 mRNA in the methylated group was decreased compared to that of the unmethylated group (P =0.032).Decitabine treatment decreased the level of p73 methylation and increased the level of p73 transcripts.Patients with p73 methylation progressed rapidly to AML (P ＜ 0.001) and had shorter survival (P =0.002) than those who did not have p73 methylation.In the multivariate Cox regression model,BM blast and p73 methylation status emerged as independent prognostic factor for overall survival and leukemia free survival.Conclusion p73 gene methylation is common in patients with MDS and may indicate poor prognosis.p73 may be a therapeutic target in MDS.
