急性髓系白血病中Nras基因点突变的检测以及信号传导通路蛋白的表达  

Research on Nras gene mutation detection and signal transduction protein expression in acute myelocytic leukemia

作　　者：杨建刚[1] 孙雪梅[2] 顾香芳[2] 徐祖琼[2] 

机构地区：[1]东南大学临床医学院,江苏南京210009 [2]南京大学医学院附属南京鼓楼医院血液科,江苏南京210008

出　　处：《现代医学》2009年第4期273-277,共5页Modern Medical Journal

摘　　要：目的研究Nras基因在急性髓系白血病(AML)中的突变以及在AML和正常对照组中RAS蛋白下游信号传导通路上AKT、ERK1/2以及其活化形式P-AKT和P-ERK1/2的表达情况。方法应用聚合酶链反应-单链构象多态性法(PCR-SSCP)及直接测序法检测AML中Nras基因突变率,应用Western blot法检测AKT、ERK以及其活化形式P-AKT,P-ERK1/2的表达量。结果48例AML中检测到2例Nras 12突变,2例Nras 61突变,突变组P-AKT、P-ERK1/2的表达水平较正常对照组明显升高(P<0.05)。未有Nras基因突变的AML其P-AKT、P-ERK1/2的表达水平也增高,但表达不均一。结论Nras基因突变可能是AML发生发展的原因之一,其机制可能是由于突变导致编码的Ras蛋白构型改变,使其处于功能持续活化状态,从而激活了Raf/Mek/Erk和PI3K/Akt等下游信号传导通路,最终导致AML的发生。Objective To study the mutation rate of Nras gene in acute myelocytic leukemia （AML） and the effect of Nras gene on the RAS protein downriver signal conduction circuit AKT,ERK1/2 and its activation form P-AKT and the P-ERK1/2 expression in AML and the normal group. Methods Polymerase chain reaction-single strand conformation polymorphism （PCR-SSCP） and direct sequencing of AML were utilized to detect Nras gene mutation rate. Western blot was employed to detect AKT, ERK and P-AKT, P-ERK1/2 expression levels. Results In 48 patients with AML, two cases of Nras 12 mutation were detected, as well as two cases of Nras 61 mutation. In the mutation group, P-AKT, P-ERK1/2 expression levels increased significantly than normal control group （ P 〈 0.05 ）. In the cases of AML with no Nras gene mutation, the expressions of P-AKT, P-ERK1/2 also increased, but not to the uniform extent. Conclusion Nras gene mutation may play a role in the development of AML;It causes the mutations in the Ras protein coding gene, leading to structure changes and constitutive activation of Ras protein. Activated Ras protein then activates Raf/ Mek/Erk and PI3K/Akt downstream signal transduction pathways, eventually leading to the incidence of AML.

关 键 词：Nras基因 急性髓系白血病 突变 P-AKT P-ERK 

分 类 号：R733.71[医药卫生—肿瘤] Q786[医药卫生—临床医学]