Prognostic impact of Wilms tumor gene mutations in Egyptian patients with acute myeloid leukemia with normal karyotype.
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.
Magda Abdel Aziz
MA
Zidan
Howyda M
HM
Kamal Shaaban
Doaa M
DM
Elghannam
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016022:Case-Control Studies; D004534:Egypt; D005091:Exons; D005260:Female; D005787:Gene Frequency; D016162:Genes, Wilms Tumor; D006801:Humans; D059785:Karyotype; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin
Acute myeloid leukemia; Mutation; Normal karyotype; WT1; Wilm's tumor gene