Published in:
01-12-2015 | Original Article – Clinical Oncology
Wilms tumor gene single nucleotide polymorphism rs16754 predicts a favorable outcome in children with acute lymphoblastic leukemia
Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2015
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Purpose
Wilms tumor gene single nucleotide polymorphism (WT1 SNP) rs16754 has been described as a favorable risk marker in patients with acute myeloid leukemia. Subsequent studies revealed inconsistent results in both adult and pediatric patients. We analyzed its impact on clinical outcome in children with acute lymphoblastic leukemia (ALL) for the first time.
Methods
WT1 SNP rs16754 of 158 children with ALL treated according to ALL Berlin-Frankfurt-Münster treatment trials from 1990 to 2009 and 43 hematopoietic stem cell donors was analyzed by allelic discrimination. WT1 SNP status was correlated with disease characteristics and clinical outcome comparing SNP (WT1GG/AG) and wildtype (WT1AA).
Results
At least one minor allele was found in 23.4 % of patients and 34.9 % of donors (P = 0.07). Distribution of patient and disease characteristics was similar between WT1GG/AG and WT1AA. In multivariate analyses, WT1 SNP was an independent good prognostic marker for cumulative incidence of relapse (CIR WT1AA vs. WT1GG/AG HR = 3.384, P = 0.021) and event-free survival (EFS; event risk WT1AA vs. WT1GG/AG HR = 2.503, P = 0.036). Univariate subanalyses of patients who underwent an allogeneic hematopoietic stem cell transplantation revealed more significant differences in CIR (P = 0.017), EFS (P = 0.012), and overall survival (OS; P = 0.017). Donor’s WT1 SNP status did not affect outcome. We found no correlation between WT1 SNP and WT1 expression level at diagnosis (P = 0.634).
Conclusion
WT1 SNP rs16754 predicts improved CIR and EFS. Outcome differences were more prominent in transplanted children. Our findings identify WT1 SNP rs16754 as a favorable risk marker in pediatric ALL which is independent from known risk factors.