Prognostic implications of Wilms' tumor gene (WT1) expression in patients with de novo acute myeloid leukemia

Abstract

Background and objectives: The Wilms' tumor (WT1) gene is overexpressed in patients with most forms of acute leukemia. Several studies have reported the usefulness of quantitative assessment of WT1 expression as a molecular marker of minimal residual disease. However, the biological significance and the prognostic impact of WT1 overexpression in acute myeloid leukemia (AML) is still uncertain.

Design and methods: We analyzed the prognostic relevance of WT1 expression in a cohort of 77 adult patients with AML, using a real-time quantitative reverse-transcription polymerase chain reaction approach.

Results: WT1 expression was significantly higher in AML patients than in normal controls (p = 0.0001). The normalized levels of WT1 with respect to the control gene for beta-glucuronidase (GUS) in AML samples showed a median WT1/GUS ratio of 0.93 (range 0-25). We classified the patients into two groups according to this ratio. Forty patients (52%) showed a WT1/GUS ratio <or= 1 and 37 (48%) had a ratio > 1. A ratio > 1, although significantly associated with FLT3 mutations, was the strongest independent prognostic factor for disease-free survival (p = 0.004), relapse risk (p = 0.005) and cumulative incidence risk (p = 0.01). This adverse prognostic value was more evident in patients aged 60 years and younger.

Interpretation and conclusions: The WT1/GUS ratio is an independent prognostic factor for predicting relapse in patients with AML and it could be included as part of the initial evaluation to establish more defined risk groups.