Format

Send to

Choose Destination
See comment in PubMed Commons below
J Pediatr Hematol Oncol. 2008 Nov;30(11):831-49. doi: 10.1097/MPH.0b013e3181868570.

Pharmacogenetics influence treatment efficacy in childhood acute lymphoblastic leukemia.

Author information

1
Pediatric Clinic II, The Juliane Marie Centre, The University Hospital Rigshospitalet, Copenhagen, Denmark.

Abstract

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 (SNPs) 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 and 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.

PMID:
18989161
DOI:
10.1097/MPH.0b013e3181868570
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wolters Kluwer
    Loading ...
    Support Center