Asparagine synthetase (ASNS) gene polymorphism is associated with the outcome of childhood acute lymphoblastic leukemia by affecting early response to treatment

Leuk Res. 2014 Feb;38(2):180-3. doi: 10.1016/j.leukres.2013.10.027. Epub 2013 Nov 5.

Abstract

The polymorphism of 14-bp tandem repeat sequence located in the ASNS gene probably acts as a transcriptional enhancer element and leads to higher expression of the gene in carriers of more than 2 repeats (>R2). We searched for an association with disease outcome in 264 children with ALL. A multivariate proportional hazard regression model adjusted for age at diagnosis (HR (95%CI)=1.05 (1.04-1.09)) and high-risk group (HR(95%CI)=3.47 (1.74-6.88)) revealed that R3 carriers with a poor response at day 15 had an increased risk of events, HR (95%CI)=2.72 (1.06-6.96). These results suggest a conditional interaction between the ASNS polymorphism and an early response to chemotherapy among pediatric patients with ALL.

Keywords: Acute lymphoblastic leukemia; Asparaginase; Outcome; Pharmacogenetics; Polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aspartate-Ammonia Ligase / genetics*
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Genotype
  • Humans
  • Infant
  • Male
  • Polymorphism, Genetic*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Treatment Outcome

Substances

  • Aspartate-Ammonia Ligase