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A new study uses genome-wide SNSNP genotypes to identify a subset of children undergoing therapy for acute lymphoblastic leukemia that are at increased risk for relapse. Borrowing from the classical approach of admixture mapping, the work shows how genome-wide assessment of genetic ancestry can be used as a biomarker for disease outcome.
Over the last 40 years, there has been a steady improvement in survival rates for children with acute lymphoblastic leukemia (ALL), the most common form of pediatric cancer. Though it is viewed as a 'curable' cancer by some, this is not true for all children, as about 20% of affected children will suffer relapse and eventually die from this condition. For several decades, pediatric oncologists have recognized that children designated as Hispanic have a higher risk for relapse of ALL1. On page 237 of this issue2, Mary Relling and colleagues use genome-wide SNP genotypes and principal component analysis3 to explore the effects of genetic ancestry on the risk of ALL relapse (Fig. 1). They report that children estimated to have 10% or more Native American ancestry have a higher rate of relapse than children from other backgrounds, with an estimated effect roughly similar to that of self-reported Hispanic ancestry.
Admixture mapping and beyond
Today, pediatric oncologists must balance efficacy and toxicity in deciding whether to treat a child with more or less intensive therapy based on clinical parameters. The determinants for risk categorization have expanded from clinical observations, such as leukocyte count at diagnosis, age at diagnosis and ethnic background, to molecular analyses, such as DNA index, T lymphocyte lineage, the presence of specific chromosomal translocations in leukemic blasts and evidence of minimal residual disease early in therapy. The studies used by Yang et al.2 to investigate the role of genetic ancestry on treatment outcome were designed to evaluate response to late intensification of...