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HLA alleles associated with asparaginase hypersensitivity in childhood ALL: a report from the DFCI Consortium
- Source :
- Pharmacogenomics
- Publication Year :
- 2020
-
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*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.
- Subjects :
- 0301 basic medicine
musculoskeletal diseases
Male
Linkage disequilibrium
Asparaginase
endocrine system diseases
Human leukocyte antigen
HLA-DQ alpha-Chains
Cohort Studies
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
immune system diseases
Genetics
Medicine
SNP
HLA-DQ beta-Chains
Humans
Allele
skin and connective tissue diseases
Child
Exome sequencing
Pharmacology
business.industry
Haplotype
Quebec
Precursor Cell Lymphoblastic Leukemia-Lymphoma
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Child, Preschool
Immunology
Molecular Medicine
Female
business
Pharmacogenetics
HLA-DRB1 Chains
Research Article
Subjects
Details
- ISSN :
- 17448042
- Volume :
- 21
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Pharmacogenomics
- Accession number :
- edsair.doi.dedup.....1fa73ab712018e158fa832447aaed087