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J Clin Oncol. 2011 Feb 20;29(6):704-11. doi: 10.1200/JCO.2010.31.9327. Epub 2010 Dec 28.

WT1 synonymous single nucleotide polymorphism rs16754 correlates with higher mRNA expression and predicts significantly improved outcome in favorable-risk pediatric acute myeloid leukemia: a report from the children's oncology group.

Author information

  • 1Fred Hutchinson Cancer Research Center, D2-373, 1100 Fairview Ave N, Seattle, WA 98103, USA. pho@fhcrc.org

Abstract

PURPOSE:

To analyze the prevalence and clinical implications of Wilms' tumor 1 (WT1) single nucleotide polymorphism (SNP) rs16754 in the context of other prognostic markers in pediatric acute myeloid leukemia (AML).

PATIENTS AND METHODS:

Available diagnostic marrow specimens (n = 790) from 1,328 patients enrolled in three consecutive Children's Cancer Group/Children's Oncology Group trials were analyzed for the presence of SNP rs16754. SNP status was correlated with disease characteristics, WT1 expression level, and clinical outcome.

RESULTS:

SNP rs16754 was present in 229 (29%) of 790 patients. The SNP was significantly more common in Asian and Hispanic patients and less common in white patients (P < .001). SNP rs16754 was also less common in patients with inv(16) (P = .043) and more common in patients with -5/del(5q) (P = .047). WT1 expression levels were significantly higher in patients with rs16754 or with WT1 mutations compared with WT1 wild-type patients (P = .021). Five-year overall survival (OS) for patients with and without the SNP was 60% and 50%, respectively (P = .031). Prognostic assessment by risk group demonstrated that in patients with low-risk disease, OS for those with and without SNP rs16754 was 90% versus 64% (P < .001) with a corresponding disease-free survival of 72% versus 53% (P = .041).

CONCLUSION:

The presence of SNP rs16754 was an independent predictor of improved OS; outcome differences were most pronounced in the low-risk subgroup. The high prevalence of WT1 SNP rs16754, and its correlation with improved outcome, identifies WT1 SNP rs16754 as a potentially important molecular marker of prognosis in pediatric AML.

PMID:
21189390
[PubMed - indexed for MEDLINE]
PMCID:
PMC3056655
Free PMC Article

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