p57kip2在初发MDS患者的表达及与SDF-1/CXCR4信号的关系  

Expression of p57kip2 in Patients with de novo Myelodysplastic Syndrome and Its Relationship with SDF-1/CXCR4 Axis

作　　者：赵佑山[1] 郭娟[2] 杨瑞[1] 顾树程[2] 张曦[2] 周立宇[2] 李晓[2] 常春康[2] 

机构地区：[1]苏州大学,江苏苏州215123 [2]上海交通大学附属第六人民医院血液科,上海200233

出　　处：《中国实验血液学杂志》2012年第2期352-357,共6页Journal of Experimental Hematology

摘　　要：本研究旨在探讨初发骨髓增生异常综合征(MDS)患者抑癌基因p57kip2的表达及其与SDF-1/CXCR4信号的关系在MDS发病中的作用。应用实时荧光定量PCR检测67例初发MDS患者骨髓单个核细胞中p57kip2及CXCR4的表达,流式细胞术检测MDS患者骨髓CD34+细胞百分比,并选择18例正常人骨髓作为对照。在体外实验中探讨SDF-1/CXCR4信号对p57kip2表达的影响,比较其作用在正常及MDS患者中的差异。结果表明,MDS患者p57kip2表达均显著低于正常对照组(P<0.001),且与骨髓CD34+细胞百分比呈负相关(r=-0.458,P<0.001),染色体核型异常MDS患者p57kip2表达低于正常核型者(P=0.045);CXCR4的表达在MDS患者及对照组间无统计学差异,但与p57kip2表达呈正相关(r=0.652,P<0.001)。正常人中,SDF-1剂量依赖性地促进骨髓单个核细胞中p57kip2的表达,该作用能被AMD3100阻断;而在MDS患者BMMNC中,SDF-1不能诱导p57kip2表达增加。结论:抑癌基因p57kip2在初发MDS患者中低表达,可能与MDS发病相关。This study was purposed to explore the expression of p57kip2 in the bone marrow of patients with de novo myelodysplastic syndrome（MDS） and its role in MDS pathogenesis,as well as the relationship between the expression of p57kip2 and SDF-1/CXCR4 signal.The expression of p57kip2 and CXCR4 in 67 de novo MDS patients was measured by real-time quantitative PCR.The percentage of CD34＋ cells in the bone marrow from MDS patients was measured by flow cytometry.18 healthy volunteers were recruited for control.The effect of SDF-1 on p57kip2 expression in bone marrow mononuclear cell（BMMNC） from MDS or normal controls was investigated in vitro,and difference between them was compared.The results showed that low-risk MDS and high-risk MDS displayed a significant reduction of p57kip2 mRNA expression in BMMNC compared with that in control group（P0.001） and there was a negative correlation between p57kip2 expression and percentage of CD34＋（r=-0.458,P0.001）;the patients with abnormal karyotype showed lower expression of p57kip2 gene,compared to patients with normal karyotype（P=0.045）.Although the expression of CXCR4 had no difference between MDS patients and normal controls,a positive correlation between p57kip2 and CXCR4 in MDS patients was still found（r=0.609,P0.001）.Moreover,SDF-1 increased p57kip2 expression in normal BMMNC in dose-dependent manner,but BMMNC from MDS patients showed no response to SDF-1.SDF-1-induced p57 expression was blocked by AMD3100.It is concluded that the low expression of p57 gene in MDS may play a role in the pathogenesis of MDS.Furthermore,SDF-1-induced p57kip2 expression in BMMNC,and the decreasing response of BMMNC to SDF-1 may contribute to the low expression of p57kip2 in MDS patients.

关 键 词：P57KIP2 骨髓增生异常综合征 基质细胞衍生因子-1 CXCR4 

分 类 号：R733.3[医药卫生—肿瘤]