Prognostic significance of Wilms' tumor gene 1 expression in children with B-cell precursor acute lymphoblastic leukemia.

INTRODUCTION

The prognostic role of Wilms' tumor 1 (WT1) gene expression at diagnosis in children with B cell precursor acute lymphoblastic leukemia (BCP-ALL) is still controversial.

METHODS

We detected the WT1 transcript levels of 533 pediatric BCP-ALL patients using TaqMan-based real-time quantitative PCR and analyzed their clinical features.

RESULTS

The WT1 transcript levels differed among the distinct molecularly defined groups, with the highest levels in the rearrangements () group. According to the results of the X-tile software, all patients were divided into two groups: WT1/ABL ≥ 0.24% (group A) and <0.24% (group B). The proportions of patients whose age was ≥10 years old, with immunophenotype of Pro-B, belonging in high-risk group, or with minimal residual disease (MRD) ≥ 0.01% at week 12 were significantly higher in group A than in group B. In the B-other group, WT1 overexpression was an independent risk factor of overall survival (OS) rate ( = 0.042), and higher MRD ≥ 0.01% at week 12 was associated with lower OS rate (<0.001) and event-free survival rate (<0.001). Moreover, the subgroup analysis revealed that, in patients with initial WBC<50 × 10/L or MRD<0.1% at day 33 or MRD<0.01% at week 12 or in the standard-risk group, WT1 overexpression led to a poorer outcome in comparison with those with WT1 downexpression (<0.05).

DISCUSSION

Therefore, pediatric BCP-ALL with WT1 overexpression had unique clinico-pathological characteristics and poor treatment response. In B-other patients, WT1 overexpression at diagnosis predicted an inferior prognosis. The WT1 gene may serve as a biomarker for monitoring residual disease in the B-other population, especially in children in the standard-risk group.