TY - JOUR

T1 - Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

AU - Devidsen, M.L.

AU - Dalhoff, K.

AU - Schmiegelow, K.

N1 - 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

PY - 2008

Y1 - 2008

N2 - 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

AB - 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

M3 - Journal article

VL - 30

SP - 831

EP - 849

JO - Journal of Pediatric Hematology/Oncology

JF - Journal of Pediatric Hematology/Oncology

SN - 1077-4114

IS - 11

ER -