Analysis of mutational status, SNP rs16754, and expression levels of Wilms tumor 1 (WT1) gene in acute promyelocytic leukemia

Abstract

Overexpression, polymorphisms, and mutations of the WT1 gene have been reported in several human tumors including acute myeloid leukemia (AML) and variably correlated with prognosis. Acute promyelocytic leukemia (APL) represents the AML subset disclosing higher WT1 expression levels; however, no WT1 studies specifically focused on APL have been conducted. We screened for the presence of mutations, SNP rs16754, and expression levels of WT1 gene in 103 adult patients with newly diagnosed APL. Fms-like tyrosine kinase (FLT3) mutations were analyzed as well. WT1 mutations were identified in four (4 %) patients. At least one copy of the minor SNP rs16754 allele (WT1(AG) or WT1(GG)) was detected in 30 (29 %) patients. Six patients (6 %) were homozygous for the minor allele (WT1(GG)) and this genotype was associated with higher WT1 mRNA copies (p = 0.018). FLT3 mutations were found in 37 % of patients and correlated with high WT1 mRNA expression (p = 0.004). Patients heterozygous or homozygous for the minor allele and patients homozygous for major (WT1(AA)) allele did not differ in terms of presenting features. In adult APL, WT1 gene mutational and polymorphic profile shows similarities with pediatric AML rather than with adult AML.

Wilms Tumor 1 rs16754 predicts favorable clinical outcomes for acute myeloid leukemia patients in South Chinese population

“…Importantly, we found that the patients carrying the WT1 GG genotype showed significantly higher WT1 mRNA expression than those with the WT1 GA/AA genotype, which is consist with several previous reports [22,26,40]. The exact mechanisms by which the rs16754 polymorphism functions remain unknown.…”

Wilms’ tumor 1 gene expression levels in acute promyelocytic leukemia compared to other acute myeloid leukemia subtypes

“…Also in our experience the distribution of bcr-type is similar to Gaur's data, without a significant correlation between bcr-type and WT1 expression levels [12] We do not know the causes of this higher expression of WT1 in APL compared to other AML subtypes, but it may be hypothesized that it could be related with the remarkable homogeneity of the leukaemic blast cells of APL [6][7][8]12]. In conclusion, according to Marlton "clarity remains still elusive" regarding the biologic effects of For personal use only.…”

Early Death in Two Patients with Acute Promyelocytic Leukemia Presenting the bcr3 Isoform, FLT3-ITD Mutation, and Elevated WT1 Level

“…APL represents the AML subtype with the highest WT1 expression levels. A recent study found that high WT1 mRNA expression correlated with the presence of FLT3 mutations, but whether this finding had an impact on clinical cure and/or outcome was unclear [8]. …”