Pharmacogenomics of acute lymphoblastic leukemia

Abstract

Purpose of review: The cure rate in children with acute lymphoblastic leukemia now exceeds almost 80% in most treatment protocols in industrialized countries. This has mainly been achieved empirically through carefully controlled, randomized clinical trials. Due to relative nonspecific action and narrow therapeutic indices of antileukemic medications, however, current therapy can be associated with significant short and long-term adverse effects, and around 20% of patients will not be cured despite intensified treatment. Pharmacogenomics, which studies the role of inheritance in individual variation in drug disposition and response, could be a useful tool to further improve outcome in this heterogeneous disease by individualization of therapy based on information gained from the genetic 'make-up' of normal host cells and lymphoblastic leukemia cells.

Recent findings: The focus of this review is on recent progress in the field by discussing the results of selected studies in which information from functional genomics, high-throughput molecular analyses, and pharmacodynamics has been integrated to establish pharmacogenomic models. These models may be used to both maximize efficacy and minimize toxicity of existing antileukemic medications, or to identify novel therapeutic targets in lymphoblasts that are resistant to conventional antileukemic drugs.

Summary: The findings from recent pharmacogenomic studies can be integrated into decision-making in future clinical trials. Thus there is great promise for advancing event-free survival in childhood leukemia in the future.