Among children with acute myeloid leukemia (AML), the presence of a specific genetic marker known as WT1 SNP rs16754 may be associated with reduced chemotherapy-related toxicity and reduced treatment-related toxic deaths if they are African American or Asian, a phase 2 Children’s Oncology Group trial suggested.
The WT1 gene, a tumor suppressor that regulates cell growth, can be subject to loss-of-function mutations that lead to the development of AML. Researchers have recently discovered that a certain single nucleotide polymorphism (SNP, a naturally occurring variation in DNA)—SNP rs16754 in the WT1 gene—is correlated with improved outcomes in pediatric patients with AML. The frequency of this SNP varies by race/ethnicity.
The study examined how the presence of SNP rs16754, which was observed in 28% overall, affected outcomes and treatment-related mortality in 492 young AML patients of different races/ethnicities. Patients who were SNP-positive had higher 5-year overall survival rates than did those who were not (61% vs 44%, respectively). Among African Americans and Asians, SNP-positive patients had significantly lower treatment-related mortality rates than did SNP-negative patients: 0% versus 25% for African Americans and 0% versus 43% for Asians, respectively. These results suggest that the protective effect of the presence of SNP rs16754 in reducing chemotherapy-related toxicity in pediatric patients with AML is more pronounced among these racial/ethnic groups than among whites.
Ho PA, Alonzo TA, Gerbing RB, et al. WT1 sp rs16754 genotype predicts treatment related mortality (TRM) in African-American and Asian pediatric AML patients: a report from the Children’s Oncology Group. Presented at: 54th American Society of Hematology Annual Meeting; December 8-11, 2012; Atlanta, GA. Abstract 1385.