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Wilms tumor 1 gene mutations are associated with a higher risk of recurrence in young adults with acute myeloid leukemia
Author(s) -
Renneville Aline,
Boissel Nicolas,
Zurawski Virginie,
Llopis Laura,
Biggio Valéria,
Nibourel Olivier,
Philippe Nathalie,
Thomas Xavier,
Dombret Hervé,
Preudhomme Claude
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24442
Subject(s) - cebpa , medicine , npm1 , oncology , myeloid leukemia , wilms' tumor , cytogenetics , karyotype , mutation , gastroenterology , gene , biology , genetics , chromosome
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 α ( 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. Cancer 2009. © 2009 American Cancer Society.