【摘要】 目的:研究VEGF、NRas和pERK1/2在急性髓系白血病(AML)中的表达及临床意义,探讨白血病发展过程中VEGF的表达与Ras/MAPK信号通路之间的相互关系。方法:应用免疫组织化学染色法检测骨髓单个核细胞VEGF、NRas和pERK1/2蛋白的水平,应用PCR/RFLP、PCRSSCP和DNA测序方法对初诊和完全缓解(CR)AML患者进行Nras基因12位点突变分析。结果:检测AML46例,在初诊组28例AML中,VEGF、Nras和pERK1/2的表达[(52.1±0.31)%、(59.8±0.32)%和(41.9±0.38)%]显著高于20例对照组[(20.5±0.16)%、(20.9±0.12)%和(14.1±0.14)%],P=0.034、P=0.008和P=0.005。CR组18例AML患者中,VEGF、NRas和pERK1/2的表达[(18.6±0.18)%、(28.2±0.27)%和(15.1±0.19)%]与对照组差异无统计学意义,P>0.05、P=0.411和P=0.343。初诊组VEGF、Nras和pERK1/2的表达较CR组显著增高,P=0.029、P=0.018和P=0.008。初诊和CR组中未发现Nras基因12位点突变。VEGF与Nras和pERK1/2表达水平相关性分析结果表明,VEGF的表达与NRas和pERK1/2的表达具有密切相关性(VEGF与NRas:r=0.510,P=0.003;VEGF与pERK1/2:r=0.513,P=0.003;VEGF与pERK1/2:r=0.464,P=0.009)。结论:VEGF和NRas/ERK信号传导通路共同参与了AML的发展过程,NRas/ERK信号传导通路的工作状态与Nras基因突变关系不密切。更多还原

【Abstract】 OBJECTIVE: To investigate the expression of VEGF, N-Ras and pERK1/2,in order to clarify the relationship between the expression of VEGF and N-Ras/ERK signal pathway in the development of human acute myeloid leukemia(AML). METHODS: The expression level of VEGF, N-Ras and pERK1/2 was checked in the samples of bone marrow mononuclear cells from 46 diagnosed AML patients using immunohistochemistry method, and mutation analysis at N-ras codon 12 was finished using the method of PCR/RFLP, PCR/SSCP and DNA sequencing analysis. RESULTS: The expression of VEGF, N-Ras and pERK1/2 were significantly higher in 28 cases of newly diagnosed AML patients [(52.1±0.31)%,(59.8±0.32)%,(41.9±0.38)%,respectively] than that of 20 cases of normal control [(20.5±0.16)%,(20.9±0.12)%,(14.1±0.14)%;P=0.034,P=0.008,P=0.005, respectively],and that of 18 cases of complete remission AML(CR AML)[(18.6±0.18)%,(28.2±0.27)%,(15.1±0.19)%;P=0.029, P=0.018 ,P=0.008,respectively]; meanwhile, there was no significant different for the expression level of VEGF, N-Ras and pERK1/2 between the group of CR AML and normal control (P>0.05, P=0.411, P=0.343). There was no mutation at N-ras codon 12 in all of patients suffering from AML. Close relationship was founded between the expression of VEGF, N-Ras and pERK1/2 (VEGF & N-Ras:r=0.510,P=0.003;VEGF & pERK1/2:r=0.513,P=0.003;VEGF & pERK1/2:r=0.464,P=0.009). CONCLUSIONS: VEGF, cooperating with N-Ras/ERK signal pathway play some roles, and N-Ras/ERK signal pathway was seldom affected, if not all, by N-ras mutation, in the development of human acute myeloid leukemia.更多还原