急性髓系白血病中HtrA2和WT1基因的表达

摘要

Objective of this study was to detect the expression of HtrA2 and WT1 mRNA in acute myeloid leukemia (AML) and investigate the relationship of their expression levels with clinical variates and correlation between them. The expression levels of HtrA2 and WT1 were measured by RQ-PCR in bone marrow cells in 104 newly diagnosed AML patients and leukemia cell lines (K562, HL-60, NB4, Kasumi-1 ,U937), and the relationship between expression level and clinical parameters (age, sex, WBC count, diagnosis and prognosis) was investigated. The results showed that (1) the expression of HtrA2 gene in newly diagnosed AML was lower than that of the normal controls (P < 0.01), while expression of WT1 gene in newly diagnosed AML was higher than that of the normal controls ( P < 0. 01), the expression levels of HtrA2 and WT1 genes both did not correlate with age, sex and WBC counts of patients. There were no significant difference of HtrA2 gene expression between different NCCN prognosis group, while WT1 gene expression in better-risk group was significantly lower than that in intermediate-risk group (P = 0.003 ). The HtrA2 expression level rised after treatment in both CR group and non-CR group(P <0.05) , while WT1 expression level significantly decreased after treatment only in CR group (P <0.01). Negative correlation between HtrA2 and WT1 expression was also observed ( r = - 0. 249, P = 0. 011). It is concluded that the low expression of HtrA2 and high expression of WT1 are closely related with occurrence and development of acute leukemia, so up-regulating expression of HtrA2 and interfering expression of WT1 may become the targets for leukemia therapy in the future.%本研究通过检测HtrA2和WT1基因在急性髓系白血病(AML)患者骨髓单个核细胞及细胞系中的表达,探讨其表达水平与临床变量的关系及二者之间的相关性.应用RQ-PCR方法检测104例初诊AML患者的HtrA2和WT1基因表达水平；比较其表达量与正常对照的差别,并分析与年龄、性别、白细胞计数、诊断分型、预后分型及治疗疗效的关系；比较治疗前后表达量的变化,分析HtrA2与WT1二者相关性.结果表明:AML患者骨髓细胞中HtrA2表达量显著低于正常对照组(P＜0.01),而WT1则显著高于正常对照组(P＜0.01)；二者表达量与患者年龄、性别、白细胞计数无关；HtrA2在不同的NCCN预后分组中表达量无显著差异,而WT1在预后良好组表达量明显低于预后中等组(P=0.003)；无论完全缓解(CR)组还是非完全缓解(non-CR)组HtrA2表达量在治疗后均显著高于治疗前(P＜0.05),而WT1表达量只有在CR组治疗后才低于治疗前(P＜0.01),non-CR组治疗后虽然也低于治疗前,但差异无统计学意义；HtrA2与WT1的表达水平呈弱负相关(r=-0.249,P=0.011).结论:HtrA2和WT1表达与白血病的发生、发展密切相关,二者表达水平呈负相关,上调HtrA2基因的表达和干扰WT1基因的表达有望成为白血病治疗的靶点.