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

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 polymor-phisms (SNPs) inGRIA1 andGALNT10 genes were genotyped. Patients withGRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity com-pared 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 ofGRIA1 (rs2055083 and rs707176) were associated significantly with the occur-rence 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 associ-ation of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants ofGRIA1might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect