WT1 mutation in 470 adult patients with acute myeloid leukemia: Stability during disease evolution and implication of its incorporation into a survival scoring system
Journal
Blood
Journal Volume
115
Journal Issue
25
Pages
5222-5231
Date Issued
2010
Author(s)
Liu C.-Y.
Tseng M.-H.
Huang C.-F.
Chiang Y.-C.
Lee F.-Y.
Liu M.-C.
Abstract
The impact of WT1 mutations in acute myeloid leukemia (AML) is not completely settled. We aimed to determine the clinical implication of WT1 mutation in 470 de novo non-M3 AML patients and its stability during the clinical course. WT1 mutations were identified in 6.8% of total patients and 8.3% of younger patients with normal karyotype (CN-AML). The WT1 mutation was closely associated with younger age (P < .001), French-American-British M6 subtype (P = .006), and t(7; 11)(p15;p15) (P = .003). Multivariate analysis demonstrated that the WT1 mutation was an independent poor prognostic factor for overall survival and relapse-free survival among total patients and the CN-AML group. A scoring system incorporating WT1 mutation, NPM1/FLT3-ITD, CEBPA mutations, and age into survival analysis proved to be very useful to stratify CN-AML patients into different prognostic groups (P < .001). Sequential analyses were performed on 133 patients. WT1 mutations disappeared at complete remission in all WT1-mutated patients studied. At relapse, 3 of the 16 WT1-mutated patients who had paired samples lost the mutation and 2 acquired additional mutations, whereas 3 of 110 WT1-wild patients acquired novel mutations. In conclusion, WT1 mutations are correlated with poor prognosis in AML patients. The mutation status may be changed in some patients during AML progression. ? 2010 by The American Society of Hematology.
Other Subjects
anthracycline; cytarabine; idarubicin; CCAAT enhancer binding protein; CD135 antigen; CEBPA protein, human; FLT3 protein, human; nuclear protein; nucleophosmin; WT1 protein; acute granulocytic leukemia; acute leukemia; adolescent; age; aged; article; cancer regression; cancer relapse; cancer survival; correlation analysis; disease course; drug megadose; female; gene mutation; human; karyotype; major clinical study; male; marker gene; multiple cycle treatment; multivariate analysis; overall survival; priority journal; prognosis; relapse; scoring system; sequential analysis; stratification; tumor suppressor gene; acute granulocytic leukemia; adult; disease free survival; genetics; middle aged; mortality; mutation; recurrent disease; retrospective study; survival rate; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; CCAAT-Enhancer-Binding Proteins; Disease-Free Survival; Female; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Nuclear Proteins; Recurrence; Retrospective Studies; Survival Rate; WT1 Proteins
Type
journal article