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Prevalence and prognostic implications of WT1 mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group
- Source :
- Blood. 116:702-710
- Publication Year :
- 2010
- Publisher :
- American Society of Hematology, 2010.
-
Abstract
- Recent studies of WT1 mutations in acute myeloid leukemia (AML) mostly report an association with unfavorable clinical outcome. We screened 842 patients treated on 3 consecutive pediatric AML trials for WT1 zinc-finger mutations. Eighty-five mutations were detected in 70 of 842 patients (8.3%). Mutations occurred predominantly in exon 7 (n = 74) but were also found in exons 8 (n = 5) and 9 (n = 6). Normal karyotype was observed in 35.3% of WT1mut patients, whereas 27.5% WT1mut patients harbored favorable risk cytogenetics. Patients with or without mutations had similar rates of complete remission after one course of induction chemotherapy. Overall survival (OS) for patients with WT1 mutations was 41% versus 54% for those without mutations (P = .016). Corresponding event-free survival (EFS) was also significantly worse for those with WT1 mutations (28% vs 42%; P = .01). However, FLT3/ITD was present in 36% of the WT1mut cohort; WT1mut patients without FLT3/ITD had similar OS (56% vs 56%, respectively; P = .8) and EFS (35% and 44%, respectively; P = .34) to patients who were wild type for both mutations. In current risk stratification schemes incorporating cytogenetics and FLT3/ITD status, the presence of WT1 mutations has no independent prognostic significance in predicting outcome in pediatric AML. The clinical trials are registered at www.clinicaltrials.gov as #NCT00002798 and #NCT00070174.
- Subjects :
- Male
Genes, Wilms Tumor
Adolescent
Clinical Trials and Observations
DNA Mutational Analysis
Immunology
Kaplan-Meier Estimate
Biochemistry
Cohort Studies
Young Adult
Prevalence
Humans
Medicine
Child
Proportional Hazards Models
Retrospective Studies
business.industry
Pediatric acute myeloid leukemia
Infant, Newborn
Infant
DNA, Neoplasm
Exons
Cell Biology
Hematology
Prognosis
Treatment Outcome
fms-Like Tyrosine Kinase 3
Leukemia, Myeloid
Tandem Repeat Sequences
Child, Preschool
Karyotyping
Acute Disease
Mutation
Female
business
Subjects
Details
- ISSN :
- 15280020, 00064971, and 00002798
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....dc84a45ade0aaa75144b1d99d908c04a