HLA alleles associated with asparaginase hypersensitivity in childhood ALL: a report from the DFCI Consortium.

ABSTRACT

Aim: To evaluate the association between human leukocyte antigen (HLA) alleles and native Escherichia coli asparaginase hypersensitivity (AH) in children with acute lymphoblastic leukemia (ALL) who received Dana-Farber Cancer Institute treatment protocols. Patients & methods:HLA-DQA1, HLA-DRB1 and HLA-DQB1 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. Results: Two alleles in linkage disequilibrium (HLA-DRB1*0701 and DQA1*0201) were associated with AH. Additional analyses, performed to distinguish between HLA-DRB1*0701 haplotypes with and without DQB1*0202 allele, showed that the association was dependent on the presence of DQB1*0202. Conclusion: This study confirms the implication of HLA-DRB1*0701, DQA1*0201 and DQB1*0202 alleles in developing AH in childhood ALL.