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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。
Objective: To investigate the expression and clinical significance of VEGF, NRas and pERK1 / 2 in acute myeloid leukemia (AML) and to explore the relationship between VEGF expression and Ras / MAPK signaling pathway in the development of leukemia. Methods: The levels of VEGF, NRas and pERK1 / 2 in bone marrow mononuclear cells were detected by immunohistochemical staining. The Nras gene 12 loci were detected by PCR / RFLP, PCR SSCP and DNA sequencing in newly diagnosed and fully AML patients. Mutational analysis. Results: The expression of VEGF, Nras and pERK1 / 2 was significantly higher in AML group (52.1 ± 0.31%, (59.8 ± 0.32)% and (41.9 ± 0.38)%] than in 20 cases (20.5 ± 0.16)%, (20.9 ± 0.12)% and (14.1 ± 0.14)%] in the control group, P = 0.034, P = 0.008 and P = 0.005. The expression of VEGF, NRas and pERK1 / 2 in 18 AML patients in CR group was not significantly different from that in control group [(18.6 ± 0.18)%, (28.2 ± 0.27)% and (15.1 ± 0.19)%, P> 0.05, P = 0.411 and P = 0.343. The expression of VEGF, Nras and pERK1 / 2 in newly diagnosed group was significantly higher than that in CR group (P = 0.029, P = 0.018 and P = 0.008). No Nras gene 12 locus mutation was found in newly diagnosed and CR group. Correlation analysis between VEGF and Nras and pERK1 / 2 showed that the expression of VEGF was closely related to the expression of NRas and pERK1 / 2 (VEGF and NRAS: r = 0.510, P = 0.003; VEGF and pERK1 / 2: r = 0.513, P = 0.003; VEGF and pERK1 / 2: r = 0.464, P = 0.009). CONCLUSION: The development of AML is involved in both VEGF and NRas / ERK signaling pathways. The relationship between NRas / ERK signal transduction pathway and Nras gene mutation is not closely related.