Background: Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences
in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure.
These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics
aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols
based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical
Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric
patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant
Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant
in pediatric diseases.
Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of
thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization
of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority
of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic
leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia,
non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal
allograft transplantation, data are still scarce.
Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of
pharmacogenomics in pediatrics.