TY - JOUR
T1 - Clinical application of thiopurine pharmacogenomics in pediatrics
AU - Pavlovic, Sonja
AU - Kotur, Nikola
AU - Stankovic, Biljana
AU - Gasic, Vladimir
AU - Lucafo, Marianna
AU - Decorti, Giuliana
AU - Zukic, Branka
N1 - Funding Information:
This work was supported by the Ministry of Education, Science, and Technology Development, Republic of Serbia (Grant No. III41004), Italian Ministry of Health (IRCCS Burlo Garofolo), RC 10_2019. Fondo di ricerca Ateneo, Università di Trieste, FRA2018.
Publisher Copyright:
© 2020 Bentham Science Publishers.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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. Phar-macogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment pro-tocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice. 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 post-transplant care. 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 lym-phoblastic 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.
AB - 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. Phar-macogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment pro-tocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice. 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 post-transplant care. 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 lym-phoblastic 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.
KW - Acute lymphoblastic leukemia
KW - Inflammatory bowel diseases
KW - Pediatrics
KW - Personalized medicine
KW - Pharmacogenomics
KW - Thiopurine drugs
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U2 - 10.2174/1389200221666200303113456
DO - 10.2174/1389200221666200303113456
M3 - Short survey
C2 - 32124692
AN - SCOPUS:85084934017
VL - 21
SP - 53
EP - 62
JO - Current Drug Metabolism
JF - Current Drug Metabolism
SN - 1389-2002
IS - 1
ER -