Open AccessHLA alleles associated with asparaginase hypersensitivity in childhood ALL: a report from the DFCI Consortium
Author(s) -
Vincent Gagné,
Pascal St-Onge,
Patrick Beaulieu,
Caroline Laverdière,
JeanMarie Leclerc,
Thai Hoa Tran,
Stephen E. Sallan,
Doneuberg,
Lewis B. Silverman,
Daniel Sinnett,
Maja Krajinović
Publication year - 2020
Publication title -
pharmacogenomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.541
H-Index - 91
eISSN - 1744-8042
pISSN - 1462-2416
DOI - 10.2217/pgs-2019-0195
Subject(s) - allele , human leukocyte antigen , asparaginase , linkage disequilibrium , haplotype , genetics , immunology , biology , exome sequencing , medicine , leukemia , gene , lymphoblastic leukemia , antigen , mutation
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*07:01 and DQA1*02:01 ) were associated with AH. Additional analyses, performed to distinguish between HLA-DRB1*07:01 haplotypes with and without DQB1*02:02 allele, showed that the association was dependent on the presence of DQB1*02:02 . Conclusion: This study confirms the implication of HLA-DRB1*07:01 , DQA1*02:01 and DQB1*02:02 alleles in developing AH in childhood ALL.