Genetic Alterations of Wilms' Tumor 1 (WT1) Gene In Korean Patients with Normal Karyotype Acute Myeloid Leukemia

Acquired mutations of the WT1 gene have been reported in 5–10% of normal karyotype AML (NK-AML) patients. Poor prognostic impact of the mutations has been reported, but some studied found no such correlation. Recent report from Germany showed the association of single nucleotide polymorphism (SNP) rs16754 status with clinical outcomes in NK-AML (J Clin Oncol 2009; 28:578). We assessed clinical implication of WT1 gene alterations in Korean patients with NK-AML.

This study included a total of 75 patients with NK-AML. All patients received standard induction chemotherapy (‘7+3’ regimen) at the Asan Medical Center, Seoul, Korea between May 1999 and Dec 2006. WT1 exons 7 and 9 were amplified using polymerase chain reaction (PCR) and purified PCR fragments were directly sequenced. The clinico-laboratory data were retrieved from the AMC Leukemia Registry.

WT1 mutations were found in four patients (5.3%): two duplication mutations and two insertion mutations. All mutations were in exon 7 and none in exon 9. Two of four patients harboring WT1 mutation failed to achieve complete remission (CR) and died at 3.9 and 7.0 months after diagnosis of AML. One of two patients attaining CR was alive without relapse at 44.0 month and another died in CR at 4.7 months. WT1 SNP rs16754 was AA genotype (WT1^AA) in 5 (3.7%), AG (WT1^AG) in 29 (38.2%), and GG (WT1^GG) in 41 (54.7%). The findings are significantly different from those of German report (WT1^AA in 74.3%, WT1^AG in 24.1%, and WT1^GG in 1.6%) (P<0.0001). No significant difference of baseline clinico-laboratory findings was observed between different genotypes of WT1 SNP rs16754 (WT1^AA/AG vs. WT1^GG). The CR rates were similar between two SNP groups (WT1^AA/AG vs. WT1^GG, 85.3% vs. 80.5%, P=0.78). The five-year probabilities of overall (OS) and relapse-free (RFS) survival appeared to be lower in patients with WT1^GG genotype, but the differences were not statistically significant (WT1^AA/AG vs. WT1^GG; OS, 49.3% vs. 36.9%, P=0.43; RFS, 56.3% vs. 42.5%, P=0.64).

The prognostic impact of WT1 mutation in NK-AML could not be assessed in this study due to low number of patients harboring the mutation, but three of four patients died with relatively short survival duration, suggesting poor prognosis of the patients with WT1 mutation. The frequency of WT1 SNPs rs16754 in our patients was different from that of German report and survivals were not significantly different according to the SNP genotypes.

No relevant conflicts of interest to declare.