白血病·淋巴瘤
白血病·淋巴瘤
백혈병·림파류
JOURNAL OF LEUKEMIA & LYMPHOMA
2011年
11期
676-679
,共4页
范芸%史晓红%宁尚勇%周昌虎%孙亮%朱小泉%唐雷%常乃柏%杨泽
範蕓%史曉紅%寧尚勇%週昌虎%孫亮%硃小泉%唐雷%常迺柏%楊澤
범예%사효홍%저상용%주창호%손량%주소천%당뢰%상내백%양택
骨髓增生异常综合征%SFRP2基因%甲基化%外周血
骨髓增生異常綜閤徵%SFRP2基因%甲基化%外週血
골수증생이상종합정%SFRP2기인%갑기화%외주혈
Myelodysplastic syndromes%Secreted frizzled related protein 2%Methylation%Peripheral blood
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分泌型卷曲相关蛋白2( SFRP2)的甲基化状态,研究其甲基化状态与染色体核型及生存的关系.方法 应用甲基化特异性聚合酶链反应( MSP)对43例MDS患者的骨髓或外周血SFRP2基因启动子区甲基化状况进行检测,并以70例门诊普通患者外周血检测结果为对照,同时对部分患者进行随访.结果 43例MDS患者中检出10例(23.3%)SFRP2甲基化,均为半甲基化状态,70例正常对照中未检出SFRP2的甲基化,组间差异有统计学意义(x2=17.86,P< 0.0001).10例SFRP2甲基化的样本中,5例来自骨髓,5例来自外周血,其中难治性贫血(RA)3例,伴环形铁粒幼细胞增多性难治性贫血(RAS)1例,难治性血细胞减少伴多系发育异常( RCMD)2例,原始细胞过多难治性贫血(RAEB)3例,MDS不能分类(MDS-U)1例.单因素分析结果显示不同性别、年龄、染色体核型、样本来源(骨髓/外周血)、危险度(WPSS≤2及>2)间甲基化率差异无统计学意义,疾病进展与稳定组甲基化率差异亦无统计学意义(均P> 0.05).20例患者有染色体核型结果,16例进行了密切随访,3例转为急性髓系白血病( AML),死亡11例中2例为SFRP2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(x2=0.022,P> 0.05).结论 MDS患者中SFRP2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;在MDS SFRP2的甲基化检测中,外周血有较好的代表性;该组患者例数较少,尚未发现甲基化与临床预后间的相关性.
目的 瞭解骨髓增生異常綜閤徵( MDS)患者Wnt/β-catenin信號轉導通路中拮抗基因分泌型捲麯相關蛋白2( SFRP2)的甲基化狀態,研究其甲基化狀態與染色體覈型及生存的關繫.方法 應用甲基化特異性聚閤酶鏈反應( MSP)對43例MDS患者的骨髓或外週血SFRP2基因啟動子區甲基化狀況進行檢測,併以70例門診普通患者外週血檢測結果為對照,同時對部分患者進行隨訪.結果 43例MDS患者中檢齣10例(23.3%)SFRP2甲基化,均為半甲基化狀態,70例正常對照中未檢齣SFRP2的甲基化,組間差異有統計學意義(x2=17.86,P< 0.0001).10例SFRP2甲基化的樣本中,5例來自骨髓,5例來自外週血,其中難治性貧血(RA)3例,伴環形鐵粒幼細胞增多性難治性貧血(RAS)1例,難治性血細胞減少伴多繫髮育異常( RCMD)2例,原始細胞過多難治性貧血(RAEB)3例,MDS不能分類(MDS-U)1例.單因素分析結果顯示不同性彆、年齡、染色體覈型、樣本來源(骨髓/外週血)、危險度(WPSS≤2及>2)間甲基化率差異無統計學意義,疾病進展與穩定組甲基化率差異亦無統計學意義(均P> 0.05).20例患者有染色體覈型結果,16例進行瞭密切隨訪,3例轉為急性髓繫白血病( AML),死亡11例中2例為SFRP2甲基化暘性,但甲基化與非甲基化組間生存率差異無統計學意義(x2=0.022,P> 0.05).結論 MDS患者中SFRP2基因存在較高的甲基化脩飾,這可能是MDS髮病的分子機製之一;在MDS SFRP2的甲基化檢測中,外週血有較好的代錶性;該組患者例數較少,尚未髮現甲基化與臨床預後間的相關性.
목적 료해골수증생이상종합정( MDS)환자Wnt/β-catenin신호전도통로중길항기인분비형권곡상관단백2( SFRP2)적갑기화상태,연구기갑기화상태여염색체핵형급생존적관계.방법 응용갑기화특이성취합매련반응( MSP)대43례MDS환자적골수혹외주혈SFRP2기인계동자구갑기화상황진행검측,병이70례문진보통환자외주혈검측결과위대조,동시대부분환자진행수방.결과 43례MDS환자중검출10례(23.3%)SFRP2갑기화,균위반갑기화상태,70례정상대조중미검출SFRP2적갑기화,조간차이유통계학의의(x2=17.86,P< 0.0001).10례SFRP2갑기화적양본중,5례래자골수,5례래자외주혈,기중난치성빈혈(RA)3례,반배형철립유세포증다성난치성빈혈(RAS)1례,난치성혈세포감소반다계발육이상( RCMD)2례,원시세포과다난치성빈혈(RAEB)3례,MDS불능분류(MDS-U)1례.단인소분석결과현시불동성별、년령、염색체핵형、양본래원(골수/외주혈)、위험도(WPSS≤2급>2)간갑기화솔차이무통계학의의,질병진전여은정조갑기화솔차이역무통계학의의(균P> 0.05).20례환자유염색체핵형결과,16례진행료밀절수방,3례전위급성수계백혈병( AML),사망11례중2례위SFRP2갑기화양성,단갑기화여비갑기화조간생존솔차이무통계학의의(x2=0.022,P> 0.05).결론 MDS환자중SFRP2기인존재교고적갑기화수식,저가능시MDS발병적분자궤제지일;재MDS SFRP2적갑기화검측중,외주혈유교호적대표성;해조환자례수교소,상미발현갑기화여림상예후간적상관성.
Objective To investigate the methylation status in the promoter region of secreting frizzled related protein 2 (SFRP2) gene in patients with myelodyplastic sydrome (MDS) and to initially explore the relationship between the methylation of this gene and prognosis/survival time.Methods MSP method was applied to examine the promoter methylation of SFRP2 gene in 43 bone marrow or peripheral blood samples of MDS patients.As controls,70 normal peripheral blood samples from volunteers of general outpatients were examined.Then some of the patients were followed up.Results In 43 patients of MDS,10 samples (23.3 %)showed SFRP2 gene methylation,and all of them were semi-methylation status.In 70 controls,no sample showed SFRP2 gene methylation.The frequency of SFRP2 gene methylation in MDS patients was significantly higher than that in controls (x2 =17.86,P <0.0001).Of the 10 SFRP2 gene methylation samples,5 were bone marrow samples and 5 were peripheral blood samples.In this group of patients,3 patients were diagnosed as RA,1 patient was diagnosed as RAS,2 patients were diagnosed as RCMD,3 patients were diagnosed as RAEB and 1 patient was diagnosed as MDS-U.There was no significant difference between the different sample source (bone marrow or peripheral blood) for the results of the methylation status (x2 =0.912,P >0.05).Either no significant difference between the different sex,age,type,chromosome and WPSS score (all P >0.05).The progress of disease didn' t influence the methylation rate (P >0.05).16 patients accepted follow-up and 11patients died,3 patients went to AML.2 died patients showed SFRP2 gene methylation.The survival analyses showed no relationship between the methylation of this gene and survival time (x2 =0.022, P >0.05).Conclusion In this MDS group,there is a high level of methyl-modification in SFRP2 gene.The methylation of SFRP2 may be one of the molecular mechanisms that contribute to the progress of patients with MDS.The peripheral blood sample maybe a better substitute in detection of SFRP2 with MDS.