title: Wilms tumor 1 gene mutations are associated with a higher risk of recurrence in young adults with acute myeloid leukemia: a study from the Acute Leukemia French Association.
abstract: BACKGROUND
  Wilms tumor 1 (WT1) is a transcription factor that is overexpressed in most acute myeloid leukemias (AMLs). Recently, 2 groups reported that WT1 mutations occur in approximately 10% of normal karyotype AMLs and are an independent predictor of poor outcome in this subgroup of patients with AML.
  
  
  METHODS
  The authors studied a cohort of 268 young adults (ages 15-50 years) with AML who were treated on the Acute Leukemia French Association 9802 trial. WT1 exon 7 and 9 mutations were screened retrospectively by polymerase chain reaction and direct sequencing. The patients also were assessed for the presence of the fms-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD), FLT3-D835/I836, nucleophosmin 1 (NPM1), and CCAAT/enhancer binding protein alpha (CEBPA) mutations.
  
  
  RESULTS
  WT1 mutations were identified in 14 patients (5%) and were associated with a younger age (P = .02) and an FLT3-ITD (P = .03). No mutation was detected in patients who had favorable cytogenetics. Patients who had WT1 mutations had a shorter overall survival at 4 years (22% vs 56%; P = .01) and a higher risk of recurrence at 4 years (82% vs 46%; P = .0008) compared with patients who had wild-type WT1. Within the subgroup of patients who had normal karyotype AML (n = 106), WT1 mutation was identified as an independent adverse prognostic factor for the risk of recurrence.
  
  
  CONCLUSIONS
  The current results indicted that WT1 mutations represent an adverse prognostic factor in young adults with AML. Prospective trials should confirm the clinical relevance of WT1 mutations in relation to other prognostic factors in patients with AML.
authors.affiliation: Department of Hematology, University of Lille Medical School, Lille, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Renneville
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boissel
authors.forename: Virginie
authors.initials: V
authors.lastname: Zurawski
authors.forename: Laura
authors.initials: L
authors.lastname: Llopis
authors.forename: Valéria
authors.initials: V
authors.lastname: Biggio
authors.forename: Olivier
authors.initials: O
authors.lastname: Nibourel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Philippe
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D016162:Genes, Wilms Tumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D055815:Young Adult