Subgroups of paediatric acute lymphoblastic leukaemia might differ significantly in genetic predisposition to asparaginase hypersensitivity

Nóra Kutszegi, Ágnes F. Semsei, András Gézsi, Judit C. Sági, Viktória Nagy, Katalin Csordás, Zsuzsanna Jakab, Orsolya Lautner-Csorba, Krisztina Míta Gábor, Gábor T. Kovács, Dániel J. Erdélyi, C. Szalai

Research output: Contribution to journalArticle

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Abstract

L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin-Frankfurt-Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01-0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09-0.53); p = 8.48E-04 and OR = 3.02 (1.36-6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.

Original languageEnglish
Article numbere0140136
JournalPLoS One
Volume10
Issue number10
DOIs
Publication statusPublished - Oct 12 2015

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asparaginase
Asparaginase
lymphocytic leukemia
Pediatrics
Genetic Predisposition to Disease
Precursor Cell Lymphoblastic Leukemia-Lymphoma
hypersensitivity
Hypersensitivity
Polymorphism
single nucleotide polymorphism
Single Nucleotide Polymorphism
Nucleotides
Genotype
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
B-Lymphoid Precursor Cells
T-cells
risk groups
genotype
Berlin
Escherichia coli

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Subgroups of paediatric acute lymphoblastic leukaemia might differ significantly in genetic predisposition to asparaginase hypersensitivity. / Kutszegi, Nóra; Semsei, Ágnes F.; Gézsi, András; Sági, Judit C.; Nagy, Viktória; Csordás, Katalin; Jakab, Zsuzsanna; Lautner-Csorba, Orsolya; Gábor, Krisztina Míta; Kovács, Gábor T.; Erdélyi, Dániel J.; Szalai, C.

In: PLoS One, Vol. 10, No. 10, e0140136, 12.10.2015.

Research output: Contribution to journalArticle

Kutszegi, N, Semsei, ÁF, Gézsi, A, Sági, JC, Nagy, V, Csordás, K, Jakab, Z, Lautner-Csorba, O, Gábor, KM, Kovács, GT, Erdélyi, DJ & Szalai, C 2015, 'Subgroups of paediatric acute lymphoblastic leukaemia might differ significantly in genetic predisposition to asparaginase hypersensitivity', PLoS One, vol. 10, no. 10, e0140136. https://doi.org/10.1371/journal.pone.0140136
Kutszegi, Nóra ; Semsei, Ágnes F. ; Gézsi, András ; Sági, Judit C. ; Nagy, Viktória ; Csordás, Katalin ; Jakab, Zsuzsanna ; Lautner-Csorba, Orsolya ; Gábor, Krisztina Míta ; Kovács, Gábor T. ; Erdélyi, Dániel J. ; Szalai, C. / Subgroups of paediatric acute lymphoblastic leukaemia might differ significantly in genetic predisposition to asparaginase hypersensitivity. In: PLoS One. 2015 ; Vol. 10, No. 10.
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abstract = "L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin-Frankfurt-M{\"u}nster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01-0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09-0.53); p = 8.48E-04 and OR = 3.02 (1.36-6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.",
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AU - Sági, Judit C.

AU - Nagy, Viktória

AU - Csordás, Katalin

AU - Jakab, Zsuzsanna

AU - Lautner-Csorba, Orsolya

AU - Gábor, Krisztina Míta

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AU - Erdélyi, Dániel J.

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