To evaluate the association between human leukocyte antigen (HLA) alleles and native asparaginase hypersensitivity (AH) in children with acute lymphoblastic leukemia (ALL) who received Dana-Farber Cancer Institute treatment protocols. , and alleles were retrieved from available whole exome sequencing data of a subset of childhood ALL patients from Quebec ALL cohort and analyzed for an association with AH. PCR assay was developed to analyze associated alleles in the entire discovery and replication cohorts. Two alleles in linkage disequilibrium ( and ) were associated with AH. Additional analyses, performed to distinguish between haplotypes with and without allele, showed that the association was dependent on the presence of . This study confirms the implication of , and alleles in developing AH in childhood ALL.