title: Asparagine synthetase (ASNS) gene polymorphism is associated with the outcome of childhood acute lymphoblastic leukemia by affecting early response to treatment.
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.
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Diabetology, Medical University of Lodz, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Pastorczak
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Diabetology, Medical University of Lodz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Diabetology, Medical University of Lodz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Zalewska-Szewczyk
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Diabetology, Medical University of Lodz, Poland.
authors.forename: Patryk
authors.initials: P
authors.lastname: Górniak
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical University of Lublin, Lublin, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Lejman
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Diabetology, Medical University of Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Trelińska
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Diabetology, Medical University of Lodz, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Walenciak
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical University of Lublin, Lublin, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kowalczyk
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczepanski
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Diabetology, Medical University of Lodz, Poland. Electronic address: wojciech.mlynarski@umed.lodz.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001217:Aspartate-Ammonia Ligase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D001217:Aspartate-Ammonia Ligase
keywords: Acute lymphoblastic leukemia; Asparaginase; Outcome; Pharmacogenetics; Polymorphism