急性白血病患者WT1基因表达水平及其临床意义

目的：探讨WT1基因与急性髓系白血病（AML）、急性淋巴细胞白血病（ALL）患者预后的关系及其用于微小残留病（MRD）监测的可能性。方法收集58例初发AML、32例初发ALL、40例AML-完全缓解（CR）、28例ALL-CR患者及31例同期三系增生活跃患者（对照组）骨髓单个核细胞，利用荧光定量聚合酶链反应（PCR）方法检测WT1基因的表达，建立WT1基因在各组间的表达阈值，以WT1拷贝数／ABL拷贝数×100%表示WT1基因的相对表达量。结果初发AML患者与对照组间WT1基因中位相对表达量差异有统计学意义20.880%（3.550%～48.500%）比0.026%（0～0.240%），Z＝-7.74，P＜0.0001]。AML-CR患者0.102%（0～5.380%）]与初发AML患者间WT1基因中位相对表达量差异有统计学意义（Z＝-8.34，P＜0.0001）。此外，WT1基因表达高于阈值（20.880%）的AML患者第1个疗程CR率为60.7%（17／28），而表达低的患者为76.7%（23／30）。AML患者复发时WT1表达升高。与对照组相比，初发ALL患者WT1基因中位相对表达量0.350%（0.021%～10.780%）]升高（Z＝-2.58，P＜0.05），但与ALL-CR患者0.038%（0～2.800%）]相比，WT1基因中位相对表达量差异无统计学意义（P＝0.065）。结论 WT1基因在AML中的表达相对较高，其可能成为AML患者预后评估及MRD监测的有效指标，但并不适用于ALL患者。

Expression of WT1 gene in acute leukemia and its significance

Objective To explore the relationship between WT1 and prognosis of patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), and to evaluate the possibility of WT1 as a potential marker for monitoring the minimal residual disease (MRD). Methods Bone marrow mononuclear cells from 58 patients with primary AML, 32 patients with primary ALL, 40 patients with AML-complete remission (CR), 28 patients with ALL-CR and 31 patients with trilineage hyperplasia (control group) were collected. Real-time fluorescent quantitative PCR method was used to detect the expression of WT1 in all patients. The expression threshold of WT1 in each group was established. WT1 copy number/ABL copy number ratio×100%denotes the relative expression level of WT1 gene. Results Median relative expression level of WT1 in the control patients was much lower than that in primary AML patients 0.026%(0-0.240%) vs. 20.880 % (3.550 %-48.500 %), Z=-7.74, P<0.000 1]. Relative expression level of WT1 between AML-CR patients 0.102%(0-5.380%)] and primary AML patients had significant difference (Z=-8.34, P<0.000 1). Moreover, the relative expression level rate of the first course in AML patients with higher WT1 expression level (>20.880 %) was 60.7 % (17/28), while the CR rate was 76.7 % (23/30) in those with lower WT1 expression. WT1 expression was increased dramatically in recurrent AML patients. Relative expression level of WT1 was significantly higher in primary ALL patients 0.350 % (0.021 %-10.780 %)] compared with that in the control group Z=-2.58, P<0.05. There was no significant difference in relative expression level of WT1 between ALL and ALL-CR patients 0.038 % (0-2.800 %), P=0.065]. Conclusion WT1 expression level in AML patients is relatively high, which could be used as an effective index of prognosis evaluation and MRD monitoring for AML patients, but not for ALL patients.