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P15INK4B基因启动子甲基化程度与不同类型的MDS及其预后的关系探讨

To investigate the relationship between P15INK4B gene promoter methylation degree and different types of MDS and prognosis
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摘要 目的 探讨P15INK4B基因启动子甲基化程度在不同类型骨髓增生异常综合征(MDS)的差异及与预后的关系.方法 运用甲基化特异性PCR及焦磷酸盐测序技术对44例不同类型的MDS患者P15INK4B基因启动子进行甲基化频率的检测,并与MDS的临床类型及临床特征进行统计学分析.结果 骨髓增生异常综合征-难治性贫血伴原始细胞增多Ⅱ型(MDS-RAEBⅡ)的患者P15INK4B基因启动子甲基化频率为(46.89±15.41)%,较其它类型的MDS增高,差异具有统计学意义(P<0.05),其它各型MDS患者P15INK4B的启动子甲基化频率差异无统计学意义(P>0.05);患者就诊时血小板下降的程度与P15INK4B基因启动子甲基化频率增高有关(t=9.02,P<0.01),血红蛋白下降和白细胞下降程度与P15INK4B基因启动子甲基化频率无关(P>0.05);P15INK4B基因启动子甲基化频率与MDS的危险分层的关系显示,低危和极低危组之间差异无统计学意义(P>0.05),中危组、高危组及极高危组之间差异均有统计学意义(P<0.05),且二年内转变为白血病患者的P15INK4B基因启动子甲基化频率为(49.21±8.78)%,与二年内未发生白血病转变的MDS患者的P15INK4B基因启动子甲基化频率(19.64%±6.24)%比较差异具有统计学意义(P<0.05).结论 P15INK4B基因启动子甲基化频率的检测可有助于判断MDS患者的预后评估. Objective To determine the methylation level of P15INK4B gene promoter in different types of myelodysplastic syndromes (MDS) and its correlation with its prognosis.Methods Methylation frequency of the P15INK4B gene promoter in 44 cases of MDS were determined by methylation-specific polymerase chain reaction (PCR) and pyrosequencing,and its correlation with clinical classification and characteristics of MDS were statistically analyzed.Results Frequency of P15INK4B gene promoter methylation in myelodysplastic syndromes-refractory anemia with excess blasts Ⅱ (MDS-RAEB Ⅱ) patients was (46.89 ± 15.41) %,significandy higher than that in other types of MDS (P 〈 0.05),but no difference in promoter methylation frequency was detected among the other types of MDS (P 〉 0.05) ; frequency of P15INK4B gene promoter methylation was found to be correlated with decline in platelet upon diagnosis (t =9.02,P 〈 0.01),but showed no significant correlation with drop of hemoglobin or leukopenia (P 〉0.05).As for the correlation between P15INK4B gene promoter methylation and MDS risk stratification,no significant difference was detected between the low-risk and very low-risk groups (P 〉 0.05),but significant differences were detected among the medium-risk,high-risk,and very high-risk groups (P 〈 0.05).In addition,frequency of P15INK4B gene promoter methylation was (49.21 ± 8.78)% in MDS patients that developed leukemia in the following two year,significantly higher than that in MDS patients who didn't (19.64 ± 6.24) % (P 〈 0.05).Conclusions P15INK4B gene promoter methylation frequency is a valuable indicator of prognosis of MDS patients.
出处 《中国医师杂志》 CAS 2015年第9期1339-1342,共4页 Journal of Chinese Physician
基金 2011年湖南省科技厅资助项目(2011SK3016)
关键词 肿瘤抑制蛋白质类/遗传学 甲基化 骨髓增生异常综合征/遗传学 预后 Tumor suppressor proteins/GE Methylation Myelodysplastic syndromes/GE Prognosis
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参考文献11

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