Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Pharmacogenetics covers the genetic variation affecting pharmacokinetics and pharmacodynamics. and their influence on drug-response phenotypes. The genetic variation includes an estimated 15 million single nucleotide polymorphisms (SNP) and is a key determinator for the interindividual differences in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far Focus has mainly been on the widely used glucocorticosteroids, methotrexate. and thiopurines, or on metabolic pathways and transport mechanisms that are common to Several drugs, Such as the glutathione S-transferases. However, beyond the thiopurine methyltransferase polymorphisms, the candidate-gene approach has not established clear associations between polymorphisms treatment response. In the future, high-throughput, low-cost, genetic platforms will allow screening of hundreds or thousands of targeted SNPs to give a combined gene-dosage effect ( = individual SNP risk profile), which may allow pharmacogenetic-based individualization of treatment
Udgivelsesdato: 2008/11
OriginalsprogEngelsk
TidsskriftJournal of Pediatric Hematology/Oncology
Vol/bind30
Udgave nummer11
Sider (fra-til)831-849
Antal sider18
ISSN1077-4114
StatusUdgivet - 2008

Bibliografisk note

Times Cited: 0ReviewEnglishSchmiegelow, KUniv Copenhagen Hosp, Rigshosp, Pediat Clin 2, Juliane Marie Ctr, Blegdamsvej 9, DK-2100 Copenhagen, DenmarkCited References Count: 217369XKLIPPINCOTT WILLIAMS & WILKINS530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USAPHILADELPHIA

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