中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2011年
4期
254-258
,共5页
王玉春%杜欣%耿素霞%李玥莹%翁建宇%陆泽生%钟立业%邓程新%赖沛龙%黄欣
王玉春%杜訢%耿素霞%李玥瑩%翁建宇%陸澤生%鐘立業%鄧程新%賴沛龍%黃訢
왕옥춘%두흔%경소하%리모형%옹건우%륙택생%종립업%산정신%뢰패룡%황흔
骨髓增生异常综合征%DNA甲基化%聚合酶链反应
骨髓增生異常綜閤徵%DNA甲基化%聚閤酶鏈反應
골수증생이상종합정%DNA갑기화%취합매련반응
Myelodysplastic syndromes%DNA methylation%Polymerase chain reaction
目的 了解骨髓增生异常综合征(MDS)患者p15、CDH1、DAPK和HICI基因的甲基化情况,探讨其与临床特征的关系.方法 通过实时荧光定量PCR方法检测52例MDS、38例初诊AML患者和46名正常人骨髓或外周血4种基因的甲基化水平,并分析MDS患者基因的甲基化水平与其临床和实验室特征的关系.结果 MDS患者骨髓p15、CDH1、DAPK和HICI基因的甲基化水平分别为16.23±21.69、6.59±9.39、0.14±0.11和7.81±9.70,外周血为14.96±20.16、6.00±9.26、0.12±0.14和6.74±9.72,骨髓与外周血4种基因甲基化水平差异无统计学意义(P值均>0.05).MDS-RAEB Ⅰ/Ⅱ患者骨髓或外周血p15及CDH1基因的甲基化水平(分别为14.70±18.17和6.61±8.79)较MDS-RCUD/RARS/5q-(分别为1.99±1.59,1.23±1.14)、MDS-RCMD(分别为3.02±3.42和1.53±2.06)和正常对照组(分别为1.69±1.82和1.01±1.12)显著升高(P值均<0.05);各分型之间DAPK基因甲基化水平差异均无统计学意义;而HIC1基因甲基化水平仅在RAEB Ⅰ/Ⅱ(9.16±11.95)与对照组(2.49±2.26)差异有统计学意义(P=0.042).不同分型组间骨髓样本4种基因(p15、CDH1、DAPK和HICI)甲基化水平差异有统计学意义(P值分别为0.001、0.003、0.039、0.023);不同分型组间外周血样本p15及DAPK基因的甲基化水平差异有统计学意义(P值分别为0.013、0.006).p15基因甲基化水平与IPSS分型、原始细胞百分数、血小板计数有相关性;CDH1基因甲基化水平与IPSS分型、原始细胞百分数有相关性;DAPK基因甲基化水平仅与年龄有相关性;HIC1基因甲基化水平与各项指标均无相关性.结论 p15和CDH1基因是MDS中较为特征性出现的高度甲基化基因,HIC1甲基化水平从低危至高危组有升高趋势,DAPK基因虽然在各分型中均能检测到甲基化,但水平较低,而四种基因的甲基化水平与MDS疗效或预后的关系有待于进一步研究.
目的 瞭解骨髓增生異常綜閤徵(MDS)患者p15、CDH1、DAPK和HICI基因的甲基化情況,探討其與臨床特徵的關繫.方法 通過實時熒光定量PCR方法檢測52例MDS、38例初診AML患者和46名正常人骨髓或外週血4種基因的甲基化水平,併分析MDS患者基因的甲基化水平與其臨床和實驗室特徵的關繫.結果 MDS患者骨髓p15、CDH1、DAPK和HICI基因的甲基化水平分彆為16.23±21.69、6.59±9.39、0.14±0.11和7.81±9.70,外週血為14.96±20.16、6.00±9.26、0.12±0.14和6.74±9.72,骨髓與外週血4種基因甲基化水平差異無統計學意義(P值均>0.05).MDS-RAEB Ⅰ/Ⅱ患者骨髓或外週血p15及CDH1基因的甲基化水平(分彆為14.70±18.17和6.61±8.79)較MDS-RCUD/RARS/5q-(分彆為1.99±1.59,1.23±1.14)、MDS-RCMD(分彆為3.02±3.42和1.53±2.06)和正常對照組(分彆為1.69±1.82和1.01±1.12)顯著升高(P值均<0.05);各分型之間DAPK基因甲基化水平差異均無統計學意義;而HIC1基因甲基化水平僅在RAEB Ⅰ/Ⅱ(9.16±11.95)與對照組(2.49±2.26)差異有統計學意義(P=0.042).不同分型組間骨髓樣本4種基因(p15、CDH1、DAPK和HICI)甲基化水平差異有統計學意義(P值分彆為0.001、0.003、0.039、0.023);不同分型組間外週血樣本p15及DAPK基因的甲基化水平差異有統計學意義(P值分彆為0.013、0.006).p15基因甲基化水平與IPSS分型、原始細胞百分數、血小闆計數有相關性;CDH1基因甲基化水平與IPSS分型、原始細胞百分數有相關性;DAPK基因甲基化水平僅與年齡有相關性;HIC1基因甲基化水平與各項指標均無相關性.結論 p15和CDH1基因是MDS中較為特徵性齣現的高度甲基化基因,HIC1甲基化水平從低危至高危組有升高趨勢,DAPK基因雖然在各分型中均能檢測到甲基化,但水平較低,而四種基因的甲基化水平與MDS療效或預後的關繫有待于進一步研究.
목적 료해골수증생이상종합정(MDS)환자p15、CDH1、DAPK화HICI기인적갑기화정황,탐토기여림상특정적관계.방법 통과실시형광정량PCR방법검측52례MDS、38례초진AML환자화46명정상인골수혹외주혈4충기인적갑기화수평,병분석MDS환자기인적갑기화수평여기림상화실험실특정적관계.결과 MDS환자골수p15、CDH1、DAPK화HICI기인적갑기화수평분별위16.23±21.69、6.59±9.39、0.14±0.11화7.81±9.70,외주혈위14.96±20.16、6.00±9.26、0.12±0.14화6.74±9.72,골수여외주혈4충기인갑기화수평차이무통계학의의(P치균>0.05).MDS-RAEB Ⅰ/Ⅱ환자골수혹외주혈p15급CDH1기인적갑기화수평(분별위14.70±18.17화6.61±8.79)교MDS-RCUD/RARS/5q-(분별위1.99±1.59,1.23±1.14)、MDS-RCMD(분별위3.02±3.42화1.53±2.06)화정상대조조(분별위1.69±1.82화1.01±1.12)현저승고(P치균<0.05);각분형지간DAPK기인갑기화수평차이균무통계학의의;이HIC1기인갑기화수평부재RAEB Ⅰ/Ⅱ(9.16±11.95)여대조조(2.49±2.26)차이유통계학의의(P=0.042).불동분형조간골수양본4충기인(p15、CDH1、DAPK화HICI)갑기화수평차이유통계학의의(P치분별위0.001、0.003、0.039、0.023);불동분형조간외주혈양본p15급DAPK기인적갑기화수평차이유통계학의의(P치분별위0.013、0.006).p15기인갑기화수평여IPSS분형、원시세포백분수、혈소판계수유상관성;CDH1기인갑기화수평여IPSS분형、원시세포백분수유상관성;DAPK기인갑기화수평부여년령유상관성;HIC1기인갑기화수평여각항지표균무상관성.결론 p15화CDH1기인시MDS중교위특정성출현적고도갑기화기인,HIC1갑기화수평종저위지고위조유승고추세,DAPK기인수연재각분형중균능검측도갑기화,단수평교저,이사충기인적갑기화수평여MDS료효혹예후적관계유대우진일보연구.
Objective To analyze the promoter methylation levels of p15、 CDH1、 DAPK and HICI genes of patients with myelodysplastic syndrome (MDS) and explore the relationship between the level of methylation and clinical features. Methods DNA methylation levels of p15、CDH1 、DAPK and HICI in peripheral blood (PB) or bone marrow (BM) samples from 52 MDS patients were detected by real-time quantitative PCR. The correlation of the methylation level with clinical features and hematological findings was analyzed. 38 de novo AML patients and 46 normal individuals served as controls. Results The methylation levels of p15 、CDH1 、DAPK and HICI were 16.23 ± 21.69,6.59 ±9.39,0. 14 ±0. 11 and 7.81 ± 9.70 in BM,and 14.96 ± 20.16,6.00 ± 9.26,0.12 ± 0. 14 and 6.74 ± 9.72 in PB, respectively from 18 MDS patients,and the difference between BM and PB was not statistically significant (P >0.05). The methylation levels of p15 (14.70 ± 18.17) and CDH1 (6.61 ±8.79) genes in high risk (RAEB Ⅰ / Ⅱ) MDS were significantly higher than in low risk (RCMD/RARS/5q -, p15: 1.99 ± 1.59, CDH1: 1.23 ± 1.14 and RCMD, p15:3.02 ±3.42, CDH1:1.53 ±2.06) MDS or control (p15:1.69 ± 1.82, CDH1: 1.01 ± 1.12) (P <0.05).The methylation levels of DAPK gene had no difference among subtypes of MDS, and that of HIC1 gene only differed between RAEB Ⅰ / Ⅱ (9.16 ± 11.95) and control (2.49 ± 2.26) (P = 0. 042). The difference of methylation levels of p15 、CDH1 、DAPK and HICI in BM was statistically significant among subtypes of MDS (P=0. 001, 0. 003 ,0. 039,0. 023 , respectively). And so did of p15 and DAPK in PB (P=0. 013, 0.006,respectively). The methylation level of p15 and CDH1 was significantly correlated with IPSS classification and blasts percentage in BM. Conclusions p15 and CDH1 genes are special hepermethylation genes in MDS.Methylation level of HIC1 gene showed an upward tendency from low risk to high risk MDS.