Related Experiment Video
Updated: Aug 19, 2026

Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
Published on: October 17, 2025
Pharmacogenetics of outcome in children with acute lymphoblastic leukemia
Jose Claudio C Rocha1, Cheng Cheng, Wei Liu
1Department of Pharmaceutical Sciences, Saint Jude Children's Research Hospital of the University of Tennessee, Memphis 38105-2794, USA.
Abstract:
Acquired genetic characteristics of acute lymphoblastic leukemia (ALL) cells are used to individualize therapy, whereas germ line genetic characteristics generally are not. We determined whether ALL outcome was related to 16 genetic polymorphisms affecting the pharmacodynamics of antileukemic agents. Of 246 children, 116 were treated on the lower-risk (LR) and 130 on the higher-risk (HR) arms of a St Jude protocol. Patients in the HR group with the glutathione S-transferase (GSTM1) non-null genotype had greater risk of hematologic relapse (P = .03), which was further increased by the thymidylate synthetase (TYMS) 3/3 genotype (P = .03). These genotypes remained predictive in multivariate analyses (P < .001 and .003, respectively). No genotypes were predictive in the LR arm. Expression of these 2 genes in ALL blasts was lower in those with low-activity genotypes. For central nervous system relapse, among the HR group, the vitamin D receptor start site (P = .02) and intron 8 genotypes (P = .04) predisposed, whereas for LR patients the TYMS 3/3 genotype predisposed (P = .04). The GSTM1 non-null and TYMS 3/3 genotypes are plausibly linked to drug resistance. Polymorphisms interact to influence antileukemic outcome and represent determinants of response that can be used to optimize therapy.
Related Concept Videos
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacokinetics in Pediatric Patients: Drug Excretion
Pharmacogenomics: Identification of New Drug Targets
Pharmacogenetics and Pharmacogenomics: Overview
Pharmacokinetics in Pediatric Patients: Drug Metabolism

