Analysis of WT1 mutations, expression levels and single nucleotide polymorphism rs16754 in de novo non-M3 acute myeloid leukemia

Abstract

The single nucleotide polymorphism (SNP) rs16754 of the WT1 gene has been described as a possible prognostic marker in patients with acute myeloid leukemia (AML). However, the results in this field are not reproducible in different cohorts. In this study, we investigated WT1 mutations, expression levels and SNP rs16754 in a cohort of 122 adult patients with AML. As the major allele (65.6%) in a Chinese population, WT1GG was associated with younger age (≤ 60) and lower percentage of blasts than WT1GA/AA. Meanwhile, improved overall survival (OS, p = 0.035) and disease-free survival (DFS, p = 0.021) were observed in WT1GG compared with WT1GA/AA. We then found that WT1 mutation, occurring in 8% of patients with AML, did not predict clinical outcome. Finally, WT1 levels were higher in patients with WT1GG than in those with WT1GA/AA. However, high levels of WT1 (> median) predicted worse OS (p = 0.015) and DFS (p = 0.034) than low levels of WT1 (≤ median). However, further studies are required to elucidate the mechanism of why WT1GG, which was associated with higher median expression of WT1 that predicts worse OS and DFS compared to low expression of WT1, predicted better OS and DFS compared with WT1GA/AA. In summary, WT1 rs16754 and WT1 expression have a significant impact on clinical outcome in patients with AML.