The hematopoietic system is critical for the viability of the human body. Erythrocytes play the major role in tissue oxygenation, platelets keep the vasculature intact, and white cells are a primary line of defense against infectious pathogens, among their other roles. In addition, the hematopoietic system is an important component of many common diseases, including cardiovascular, central nervous system (CNS), renal, and cancer. Major advances in the treatment of hematologic disorders have resulted from the recent revolution in medical interventions. However, significant heterogeneity in the efficacy and toxicity of drugs is consistently observed across the human population (1). Administration of the same dose of a given drug to a population of patients results in a range of toxicity, from unaffected to lethal events (2,3). Although many clinical variables have been associated with drug response (age, gender, diet, organ function, disease biology), genetic differences in drug disposition and drug targets can have a great impact on treatment outcome (1,4,5). The metabolic enzymes and cellular targets for the majority of che-motherapeutic agents contain genetic polymorphisms (6), but prospective identification of patients likely to benefit from (or be harmed by) chemotherapy is not currently possible for most treatments. This is particularly important in the current health care environment, where cost containment and evidence-based initiatives are having a significant influence on patient care.

Pharmacogenomics is the study of how genetic inheritance influences response to drugs. A greater understanding of the genetic determinants of drug response has the potential to revolutionize the use of many medications, particularly in the challenging field of oncology. By increasing our ability to prospectively identify patients at risk for severe toxicity, or those likely to benefit from a particular treatment, pharmaco-genomics promises to help us move toward the ultimate goal of individualized cancer therapy. This chapter will discuss distinct clinically relevant examples of hematologic pharmacogenetics.

^The authors are supported in part by National Institutes of Health grants GM63340, R01HL074724, and R01HL071083.

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