Genetic studies in acute lymphoblastic leukemia

As the long-term event-free survival rate in children with acute lymphoblastic leukemia approaches 80%, emphasis is being placed on risk-directed therapy to prevent over- or undertreatment. It has become apparent that risk assignment based on primary genetic abnormalities is inadequate by itself, and that measurement of early responses to therapy and the extent of minimal residual disease is needed to improve the accuracy of risk classification. Studies to identify genetic polymorphisms with pharmacokinetic and pharmacodynamic significance promise to enhance the discovery of new drugs and to optimize chemotherapy. Recent successes in directing therapy to specific genetic abnormalities demonstrate the feasibility of molecular medicine for the childhood leukemias, and predict the development of highly effective drug regimens with minimal toxicity against normal hematopoietic cells.