Related Experiment Video

Updated: Apr 1, 2026

In Ovo Xenografting of Patient-Derived Acute Lymphoblastic Leukemia (ALL) Cells (PDX-ALL)
06:48

In Ovo Xenografting of Patient-Derived Acute Lymphoblastic Leukemia (ALL) Cells (PDX-ALL)

Published on: August 1, 2025

666

Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to

Nóra Kutszegi1, Ágnes F Semsei1, András Gézsi1

  • 1Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.

Plos One
|October 13, 2015
PubMed

Insights

Genetic variants in the GRIA1 gene may influence hypersensitivity reactions to L-asparaginase (ASP) in children with acute lymphoblastic leukaemia (ALL). Specific GRIA1 genotypes were associated with a reduced risk of ASP hypersensitivity in T-cell ALL patients.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Immunology

Background:

  • L-asparaginase (ASP) is a crucial chemotherapy agent for paediatric acute lymphoblastic leukaemia (ALL).
  • Hypersensitivity reactions (HSRs) to ASP pose a significant clinical challenge in treating paediatric ALL patients.
  • Identifying genetic factors influencing ASP HSRs can optimize treatment strategies.

Purpose of the Study:

  • To investigate the association between genetic variants in GRIA1 and GALNT10 genes and the risk of developing hypersensitivity reactions to Escherichia coli-derived L-asparaginase in paediatric ALL patients.

Main Methods:

  • Genotyping of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes.
  • Analysis of clinical and genetic data from 576 paediatric ALL patients.
  • Statistical analysis to determine the association between specific genotypes and ASP hypersensitivity risk.

Main Results:

  • The GRIA1 rs4958351 AA/AG genotype was linked to a significantly lower risk of ASP hypersensitivity in the T-cell ALL subgroup (OR = 0.05).
  • In the medium-risk group, GRIA1 SNPs rs2055083 and rs707176 showed significant associations with ASP hypersensitivity (ORs = 0.21 and 3.02, respectively).
  • The association of rs707176 with ASP HSRs was predominantly observed in female patients.

Conclusions:

  • Genetic variations within the GRIA1 gene may play a role in modulating the risk of L-asparaginase hypersensitivity in paediatric ALL.
  • Patient subgroups, such as T-cell ALL and females, may exhibit distinct genetic predispositions to ASP hypersensitivity.
  • Further research into GRIA1 variants could lead to personalized approaches for ASP administration in ALL treatment.

More Related Videos

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.8K
Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-Derived Xenograft Mouse Model06:08

Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-Derived Xenograft Mouse Model

Published on: February 10, 2023

1.9K

Related Concept Videos

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
68
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
62
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.3K
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
332
Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
374
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
112