The Wilms' tumor (WT1) gene mutations were detected in patients with most forms of acute leukemia. However, the biological significance and the prognostic impact of WT1 mutation in Egyptian patients with acute myeloid leukemia with normal karyotype (AML-NK) are still uncertain. We aimed to evaluate the incidence and clinical relevance of WT1 gene mutations in acute myeloid leukemia with normal karyotype (AML-NK). Exons 7 and 9 of WT1 were screened in samples from 216 adult NK-AML using polymerase chain reaction single-strand conformation polymorphism techniques. Twenty-three patients (10.6%) harbored WT1 mutations. Younger ages and higher marrow blasts were significantly associated with WT1 mutations (P = 0.006 and 0.003 respectively). Complete remission rates were significantly lower in patients with WT1 mutations than those with WT1 wild-type (P = 0.015). Resistance, relapse, and mortality rates were significantly higher in patients with WT1 mutations than those without (P = 0.041, 0.016, and 0.008 respectively). WT1 mutations were inversely associated with NPM1 mutations (P = 0.007). Patients with WT1 mutations had worse disease-free survival (P < 0.001) and overall survival (P < 0.001) than patients with WT1 wild-type. In multivariable analyses, WT1 mutations independently predicted worse DFS (P < 0.001; hazard ratio [HR] 0.036) and overall survival (P = 0.001; HR = 0.376) when controlling for age, total leukocytic count (TLC), and NPM1 mutational status. In conclusion, WT1 mutations are a negative prognostic indicator in intensively treated patients with AML-NK, may be a part of molecularly based risk assessment and risk-adapted treatment stratification of patients with AML-NK.

Objective: Somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, are the most frequent mutations in patients with acute myeloid leukemia. The aim of the study was to assess the prevalence and prognostic impact of NPM1 gene mutations in adult AML patients.Materials and Methods: Polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) were used to screen 55 AML patients for mutations of NPM1 gene.Results: NPM1 mutations were found in 12 (21.8%) of 55 patients, significantly associated with higher total leukocytie count, marrow blast percentage (p=0.03 and p=0.02, respectively), and M5 subtype (p<0.001). Patients with NPM1 mutations had significantly higher complete remission rates (p=0.003) and a trend to lower rates of mortality, relapse and refractory disease (p=0.28, p=0.45 and p=0.08, respectively). Survival analysis showed significantly longer disease-free survival (mean 18.635±1.229 versus 11.041±1.250 months, p=0.044) and overall survival (mean 19.810±1.624 versus 12.063±1.244 months, p=0.041) in patients with NPM1 mutations compared with those without. Multivariate analyses confirmed NPM1 mutation as a significant independent predictor for disease-free survival (HR=0.066, p=0.001) and overall survival (HR=0.125, p=0.002).Conclusion: NPM1 mutation is a prognostic factor for a favorable outcome in Egyptian population. This finding is of major clinical importance since it strongly suggests that NPM1 mutations may allow one to divide the heterogeneous patient group of AML into prognostically different subgroups.Conflict of interest:None declared.