Pharmacogenomics of pediatric acute lymphoblastic leukemia.
BACKGROUND
Pediatric acute lymphoblastic leukemia (ALL) represents one of the best examples of progress in disease treatment and improved outcome based in part upon the incorporation of the principles of pharmacogenomics. Throughout the past several decades, clinical scientists have continued to refine risk stratification in clinical trials with the understanding that individual patients have different subtypes of pediatric ALL that will respond to therapy in different, but predictable ways.


METHODS
Discussed in this review are the most significant findings from pharmacogenomic studies of pediatric ALL from 1989 to the present. Pharmacogenomic studies related to the drugs commonly used to treat pediatric ALL are covered in detail, including an emphasis on both genome-wide and candidate gene/pathway approaches.


RESULTS
Readers of this paper will acquire a detailed understanding of how pharmacogenomic studies can be integrated into clinical trials, in addition to some of the discrepancies still present in the field.


CONCLUSIONS
The outcome for children with pediatric ALL has improved greatly, and this is in part due to the successful integration of data from pharmacogenomic studies into clinical trials.
Meeker
Nathan D
ND
Division of Pediatric Hematology/Oncology, Department of Oncological Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
Yang
Jun J
JJ
Schiffman
Joshua D
JD
D002648:Child; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D008780:Methyltransferases / Q000235:genetics; D018365:Neoplasm, Residual; D010597:Pharmacogenetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D014750:Vincristine / Q000627:therapeutic use
D005938:Glucocorticoids; D014750:Vincristine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D008727:Methotrexate