title: WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system.
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.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Hou
authors.forename: Tai-Chung
authors.initials: TC
authors.lastname: Huang
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Chou
authors.forename: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Tseng
authors.forename: Chi-Fei
authors.initials: CF
authors.lastname: Huang
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Chiang
authors.forename: Fen-Yu
authors.initials: FY
authors.lastname: Lee
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Huang
authors.forename: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.forename: Shang-Ju
authors.initials: SJ
authors.lastname: Wu
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D025721:WT1 Proteins / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D025721:WT1 Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3