Wilms tumor 1 gene mutations are associated with a higher risk of recurrence in young adults with acute myeloid leukemia
Renneville A et al. - In a study to determine whether WT1 mutations are a predictor of poor outcome in pts with acute myeloid leukemia (AML), it was reported 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 pts with AML. Methods- 268 young adults (ages 15-50 yrs) with AML who were treated on the Acute Leukemia French Association 9802 trial were studied.
- WT1 exon 7 and 9 mutations were screened retrospectively by polymerase chain reaction and direct sequencing.
- Pts were assessed for 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 pts (5%) and were associated with a younger age and an FLT3-ITD.
- No mutation was detected in pts who had favorable cytogenetics.
- Pts who had WT1 mutations had a shorter overall survival at 4 yrs (22% vs 56%) and a higher risk of recurrence at 4 yrs (82% vs 46%) vs pts who had wild-type WT1.
- Within the subgroup of pts who had normal karyotype AML (n=106), WT1 mutation was identified as an independent adverse prognostic factor for risk of recurrence.
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