基质金属蛋白酶和Toll样受体9在急性白血病患者中的表达及意义

Expression and significance of matrix metalloproteinases and toll-like receptor 9 in patients with acute leukemia

目的探讨基质金属蛋白酶(MMP)和Toll样受体9(TLR9)在急性白血病患者中的表达及意义。方法将44例急性淋巴细胞白血病(ALL)患者纳入ALL组,将30例急性髓细胞白血病(AML)患者纳入AML组,另选取同期在医院体检的44例健康体检者纳入对照组。采用酶联免疫吸附试验(ELISA)法检测3组血清MMP-2、MMP-7、MMP-9水平,采用实时荧光定量聚合酶链反应(qRT-PCR)和蛋白质印迹法(Western blot)检测3组外周血单核细胞中TLR9 mRNA和TLR9蛋白表达情况,采用Spearman等级相关分析法分析不同临床分型急性白血病恶性程度与MMP、TLR9蛋白表达水平的相关性。结果ALL组、AML组血清MMP-2、MMP-7、MMP-9水平均高于对照组,且AML组高于ALL组,差异有统计学意义(P<0.01);ALL组、AML组外周血单核细胞中TLR9 mRNA和TLR9蛋白相对表达量均低于对照组,且AML组低于ALL组,差异有统计学意义(P<0.01)。Spearman等级相关分析结果显示,血清MMP-2、MMP-7、MMP-9水平均分别与ALL、AML恶性程度呈正相关(P<0.05),TLR9蛋白相对表达量均与ALL、AML恶性程度呈负相关(P<0.05)。结论急性白血病患者血清MMP-2、MMP-7和MMP-9水平显著升高,且外周血单核细胞中TLR9表达显著降低。MMP异常高表达可能通过抑制TLR9表达,促进急性白血病细胞的髓外浸润和免疫逃逸,进而加速肿瘤的恶性进展。

Objective To investigate the expression and significance of matrix metalloproteinases(MMPs)and toll-like receptor 9(TLR9)in patients with acute leukemia.Methods A total of 44 patients with acute lymphoblastic leukemia(ALL)were enrolled in the ALL group,30 patients with acute myeloid leukemia(AML)were included in AML group,and 44 healthy individuals undergoing physical examination during the same period were included in the control group.Serum levels of MMP-2,MMP-7,and MMP-9 were measured by enzyme-linked immunosorbent assay(ELISA)in all three groups.The expression of TLR9 mRNA and TLR9 protein in peripheral blood mononuclear cells(PBMCs)was detected by quantitative real-time polymerase chain reaction(qRT-PCR)and western blot,respectively.Spearman′s rank correlation analysis was used to explore the correlations of the malignancy of different clinical subtypes of acute leukemia with the expression levels of MMPs and TLR9 protein.Results Serum levels of MMP-2,MMP-7,and MMP-9 were significantly higher in the ALL and AML groups compared to the control group,with the AML group showing higher levels than the ALL group(P<0.01).The relative expressions of TLR9 mRNA and TLR9 protein in PBMCs in both the ALL and AML groups were significantly lower than those in the control group,and the AML group had lower expression than the ALL group(P<0.01).Spearman′s rank correlation analysis revealed positive correlations of serum levels of MMP-2,MMP-7,and MMP-9 with the malignancy of both ALL and AML(P<0.05),while the relative expression of TLR9 protein was negatively correlated with the malignancy of both ALL and AML(P<0.05).Conclusion Serum levels of MMP-2,MMP-7,and MMP-9 are significantly elevated in patients with acute leukemia,while TLR9 expression is significantly reduced in PBMCs.The abnormal overexpression of MMPs may promote extramedullary infiltration and immune escape of acute leukemia cells by inhibiting TLR9 expression,thereby accelerating the malignant progression of the tumor.