Institutional members access full text with Ovid®

Share this article on:

Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

Davidsen, Marie Louise MSc*; Dalhoff, Kim MD, DMSc; Schmiegelow, Kjeld MD* ‡

Journal of Pediatric Hematology/Oncology: November 2008 - Volume 30 - Issue 11 - p 831-849
doi: 10.1097/MPH.0b013e3181868570
Medical Progress

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.

*Pediatric Clinic II, The Juliane Marie Centre, The University Hospital Rigshospitalet

Clinical Pharmacology and Toxicology, Bispebjerg Hospital

The Medical Faculty, The Institute of Gynecology, Obstetrics, and Pediatrics, The University of Copenhagen, Copenhagen, Denmark

Supported by Ministry of Health (Grant no. 2006-12103-250), the Novo Nordisk Foundation, Danish Cancer Council for Health and Disease (Grant no. 271-06-0278), and the Danish Childhood Cancer Foundation. Kjeld Schmiegelow holds the Danish Childhood Cancer Foundation Professorship in Pediatric Oncology.

Reprints: Kjeld Schmiegelow, MD, Pediatric Clinic II, The Juliane Marie Centre, The University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark (e-mail: kschmiegelow@rh.dk).

Received for publication June 3, 2008; accepted July 11, 2008

© 2008 Lippincott Williams & Wilkins, Inc.