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-现代医学

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

单位：东南大学临床医学院; 南京大学医学院附属南京鼓楼医院血液科;

分类号：

出版年·卷·期（页码）：2009·37·第四期（273-277）

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.Result...

参考文献：

[1]	Gougopoulou DM, Kiaris H, Ergazaki M, et al. Mutations and expression of the ras family genes in leukemias .Stem Cells, 1996, 14(6) :725 .
[2]	J. P. Perentesis, S. Bhatia, E. Boyle, et al. RAS oncogene mutations and outcome of therapy for childhood acute lymphoblastic leukemia .Leukemia, 2004, 18 (4) :685-692 .
[3]	Bowen,DT,Frew,ME,Hills,R. RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years .Blood, 2005, 106 :2113~2119 .
[4]	Molina JR,Adjei AA. The Ras/Raf/MAPKpathway[J] .J Thorac Oncol, 2006, 1 (1) :7-9 .
[5]	Martelli AM,Nyakern M,Tabellini G,et al. Phosphoinositide3-kinase/Akt signaling pathway and its therapeutical implications for humanacutemyeloidleukemia[J] .Leukemia, 2006, 20 (6) :911-928 .
[6]	Chun KH,Kosm eder JW,Sun S,et al. E ffects of deguelin on thephosphatidylinositol 3-k inase/Akt pathway and apoptosis in pre-malignant human bronch ial ep ithelial cells[J] .J Natl CancerInst, 2003, 95 (4) :291-302 .
[7]	Levis M. Recent advances in the development of small-moleculeinhibitors for the treatment of acute myeloid leukemia[J] .CurrOpin Hematol, 2005, 12 (1) :55-61 .
[8]	Gilliland D G. FLT3-activating mutations in acute promyelocyticleukaemia:a rationale for risk-adapted therapy with FLT3inhibitors[J] .Best Pract&Res Clin Haematol, 2003, 16 (3) :409-417 .
[9]	Barletta G,Gorini G,Vineis P,et al. Ras gene mutations inpatients with acute myeloid leukaemia and exposure to chemicalagents[J] .Carcinogenesis, 2004, 25 (5) :749-755 .
[10]	Le D T,Shannon K M. Ras processing as a therapeutic target inhematologic malignancies[J] .Curr Opin Hematol, 2002, 9 (4) :308-315 .
[11]	Gills J J,Dennis P A. The development of phosphatidylinositolether lipid analogues as inhibitors of the serine/threoninekinase,Akt[J] .Expert Opin Investig Drugs, 2004, 13 (7) :787-797 .
[12]	Kondapaka S B,Singh S S,Dasmahapatra G P,et al. Perifosine,a novel alkylphospholipid,inhibits protein kinase Bactivation[J] .Mol Cancer Ther, 2003, 2 (11) :1093-1103 .

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录