MERIT Award Recipient: William E. Evans, Pharm.D.
Pharmacogenomics of Childhood Leukemia (ALL)
Research in the Evans lab focuses on the pharmacogenomics of childhood acute lymphoblastic leukemia (ALL), as reviewed in Evans and Relling, Science, 286: 487-491, 1999, and Evans and Relling, Nature, 429:464-468, 2004. Current research aims to identify genetic and genomic mechanisms for differences in the antileukemic effects of chemotherapy used to treat childhood ALL. Our previous studies have elucidated the genetic basis for inherited differences in thiopurine methyltransferase (TPMT), a key enzyme for metabolism of the widely used antileukemic agent mercaptopurine. Subsequent studies have identified additional genetic and epi-genetic determinants of the efficacy or toxicity of antileukemic agents. We are now using genome-wide methods, such as gene expression profiling and haplotype mapping, in addition to candidate gene strategies, to identify additional genes and polymorphisms that determine the effects of antileukemic agents used to treat children with ALL. Despite enormous improvement in the cure rate of childhood ALL, the most common cancer in children (cure rate now >80%), cancer remains the leading cause of death by disease in US children over 1 year of age, indicating the need for further progress. Human genome variability is a major source of inter-individual differences in drug response, and our work aims to identify the important genetic determinants of treatment outcome in childhood ALL.