【作者】 张秀斌；

【导师】 纪春岩；

【作者基本信息】 山东大学 ， 内科学， 2008， 硕士

【摘要】 研究背景急性髓性白血病(acute myelocytic leukemia,AML)是严重危害患者健康的造血系统恶性肿瘤,其发病机制尚不十分清楚。PTEN是第一个被发现的具有磷酸化酶功能的抑癌基因,无论是在实体瘤还是在造血系统恶性肿瘤中,均存在PTEN功能的缺失。Notch信号通路在介导造血细胞增殖与分化过程中具有重要作用。PTEN和Notch均与恶性肿瘤的发生发展密切相关,二者之间存在一定联系。近年研究显示,PTEN和Notch1在急性髓性白血病中均有一定表达,但具体作用机制及其在疾病中的相互作用有待于进一步阐明。目的通过检测AML患者外周血单个核细胞中PTEN和Notch1基因的表达情况,探讨PTEN与Notch1在AML发病过程中的相互关系,为进一步揭示AML发病机制及其分子靶向治疗提供依据。方法选取AML患者共51例,分为初诊组和完全缓解(CR)组,并以22例健康志愿者作为对照。收集AML患者及对照组外周血单个核细胞,应用实时荧光定量逆转录聚合酶链反应(realtime Q-RT-PCR)方法对标本进行PTEN和Notch1基因表达的检测,同时以β-actin为内参照。应用SPSS统计学软件处理数据,采用Wilcoxon秩和检验、Spearman相关进行统计学分析,P＜0.05为差异有统计学意义。结果1.初诊AML患者外周血单个核细胞PTEN表达显著低于对照组(P＜0.05);也低于CR组,差异无统计学意义。2.初诊AML患者外周血单个核细胞Notch1表达显著高于对照组(P＜0.05);也高于CR组,差异无统计学意义。3.CR组AML患者外周血单个核细胞PTEN表达低于对照组,差异无统计学意义。4.CR组AML患者外周血单个核细胞Notch1表达高于对照组,差异无统计学意义。5.CR组和对照组PTEN与Notchl呈显著正相关(P＜0.01)。结论1.AML患者中存在PTEN和Notch1的异常表达,且与疾病状态有关,提示二者在AML发生发展中可能起一定作用。2.AML完全缓解患者PTEN和Notch1存在相互联系。更多还原

【Abstract】 BackgroundAcute myeloid leukemia(AML)is the common hematopoietic malignancy which endangers the health of patients severely.The pathogenesis of the disorder is not very clear. PTEN is the first tumor suppressor gene with the activity of phosphorylase.The loss of PTEN can be found in both solid tumors and hematopoietic malignancies.Notch signaling pathway plays an important role in the proliferation and differentiation of hematopoietic cells.PTEN and Notch signaling are the leading causes to the development of malignant tumors,and there are some relations between of them.It is showed that abnormal expression of PTEN or Notch1 can be tested in acute myeloid leukemia in recent years,but the mechanisms and relationships in the pathogenesis of AML need to be further studied.ObjectiveTo investigate the roles and mutual relations of PTEN and Notch1 in the pathogenesis of AML,we detect the expression level of PTEN and Notch1 mRNA of AML patients’ peripheral blood mononuclear cells(PBMs),so as to reveal the pathogenesis of AML and provide the basis for molecular targeted therapy.MethodsWe selected 51 AML patients,divided into the newly diagnosed group and the complete remission(CR)group,and selected 22 healthy volunteers as control group.Collecting peripheral blood mononuclear cells of AML patients and the control group,and using the real-time Q-RT-PCR to detect the mRNA expression of PTEN and Notch1,andβ-actin were detected as internal control.We used SPSS statistical software,and Wilcoxon rank-sum test and Spearman rank correlation was applied.P＜0.05 is the statistical significance differences.Results1.The expression of PTEN in peripheral blood mononuclear cells of newly diagnosed group patients were significantly lower than that of the control group(P＜0.05);and also lower than that of CR group,but there was no significant difference.2.The expression of Notch1 in peripheral blood mononuclear cells of newly diagnosed group patients were significantly higher than that of the control group(P＜0.05);and also higher than that of CR group,but there was no significant difference.3.The expression of PTEN in peripheral blood mononuclear cells of CR group patients was decreased,but there was no significant difference.4.The expression of Notch1 in peripheral blood mononuclear cells of CR group patients was increased,but there was no significant difference.5.PTEN and Notch1 in CR group and control group were positive correlation(P＜0.01).Conclusions1.The abnormal expression of PTEN and Notch1 could be found in AML patients,and be related to the disease status,suggesting that they may both play important roles in the development of AML.2.PTEN and Notch1 are interrelated in AML patient with complete remission.更多还原