Pharmacogenetics and Personalized Medicine in Hematology

Excerpt

Genetic variation among human beings has a significant impact on disease susceptibility as well as treatment outcomes. It is now recognized that the human genome, despite its 99.5% sequence homology within the species, is unique for every individual because of the thousands of single nucleotide polymorphisms, insertion-deletion mutations and copy number variations as well as alternative splicing patterns and variable gene expression profiles that individuals display [1]. This genetic heterogeneity is often imperceptible at the phenotypic level in healthy persons, but research has revealed its associations with several diseases like diabetes mellitus and many cardiac, neurological and psychiatric illnesses [2]. It also has major implications in hematological disorders, and precision and personalized medicine is considered one of the frontier areas of translational research today. Salient examples include the incorporation of CYP2C9 and VKORC1 genotypes in oral anticoagulant dosing algorithms and the influences of thiopurine S-methyltransferase (TPMT) and methylene tetrahydrofolate reductase (MTHFR) genotypes on the safety and efficacy of 6-mercaptopurine and methotrexate therapies respectively in acute lymphoblastic leukemia [3]. …