Recent advances in childhood acute lymphoblastic leukemia

Contemporary risk-directed therapy has advanced the cure rate for childhood acute lymphoblastic leukemia to near 80%. Molecular genetic analyses of leukemic cells, pharmacodynamic studies of antileukemic agents, and pharmacogenetic studies of the host's drug-metabolizing enzymes, drug transporters, and drug targets are providing a rational base for further improvement of treatment efficacy and the reduction of complications. Early treatment response, as defined by the measurement of minimal residual disease, which reflects both the drug responsiveness of leukemic cells and host pharmacodynamics/pharmacogenomics, is the most reliable prognostic indicator for gauging the intensity of treatment. Recent advances in high-throughput biotechnology, including gene expression profiling, proteomics and gene silencing promise to identify molecular targets for specific treatment. The ultimate goal is to elucidate central mechanisms of leukemogenesis so that preventive measures can be devised.