儿童急性髓细胞白血病WT1基因表达及其临床意义

Expression of WT1 gene in children with acute myeloid leukemia

摘要:

目的 研究急性髓细胞白血病（AML）患儿WT1基因表达情况及其与临床预后的关系。方法 采用实时荧光定量PCR方法检测45例非M3儿童AML的WT1表达水平，并回顾性分析其与AML预后的关系。结果 骨髓幼稚细胞比例 > 60%的AML患儿WT1表达水平高于幼稚细胞≤60%的患儿（P < 0.05）。M2病例组初诊时WT1表达量低于非M2病例组（P < 0.05）。完全缓解组患儿的WT1表达量显著低于初诊组和复发组（P < 0.01）。诱导化疗结束时WT1高表达组的2年无病生存率（DFS）低于WT1低表达组（P < 0.05）。诱导化疗结束时WT1下降程度≥1个数量级病例组的2年总生存率（OS）和DFS高于WT1下降程度 < 1个数量级病例组（P < 0.05）。AML患儿骨髓复发2~3个月前WT1表达呈上升趋势。结论 WT1表达水平与儿童AML预后密切相关，动态监测WT1表达在指导儿童AML个体化治疗、预后评估和复发预测方面具有重要临床应用价值。

Abstract:

Objective To study WT1 gene expression in children with acute myeloid leukemia (AML) and its possible correlations to clinical outcomes. Methods Bone marrow samples were collected from 45 children with AML (excluding acute promyelocytic leukemia, AML-M3) at different time points of AML treatment and follow-up. WT1 gene expression levels in bone marrow mononuclear cells were assayed by real-time fluorescence quantitative PCR. The correlation between WT1 expression and prognosis was retrospectively analyzed. Results The WT1 expression level in AML children with bone marrow blast cell percentage of > 60% was significantly higher than in those with bone marrow blast cell percentage of ≤ 60% (P < 0.05). The lower WT1 expression level was documented in children with AML-M2 compared with in children with other non-M2 subtypes (P < 0.05). WT1 expression level in patients in complete remission was significantly lower than that in patients at diagnosis or relapse (P < 0.01). The 2-year disease-free survival (DFS) in patients with higher WT1 expression was significantly lower than in those with lower WT1 expression at the end of induction chemotherapy (P < 0.05). The 2-year overall survival (OS) and DFS in patients with ≥1 log WT1 reduction range were significantly higher than those with < 1 log reduction of WT1 expression level at the end of induction chemotherapy (P < 0.05). WT1 expression levels tended to rise 2-3 months prior to bone marrow relapse. Conclusions WT1 expression level is closely correlated prognosis in children with AML. Dynamic monitoring of WT1 expression level is of great clinical importance in terms of individualized management, prognosis evaluation and relapse prediction.