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. 2020 Jun;21(8):541-547.
doi: 10.2217/pgs-2019-0195. Epub 2020 May 6.

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

Vincent Gagné  1 , Pascal St-Onge  1 , Patrick Beaulieu  1 , Caroline Laverdière  1   2 , Jean-Marie Leclerc  1   2 , Thai H Tran  1   2 , Stephen E Sallan  3   4 , Donna Neuberg  5 , Lewis B Silverman  3   4 , Daniel Sinnett  1   2 , Maja Krajinovic  1   2   6
Affiliations

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

Vincent Gagné et al. Pharmacogenomics. 2020 Jun.

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.

Keywords: SNP; acute lymphoblastic leukemia; asparaginase; asparaginase hypersensitivity; human leukocyte antigen; pharmacogenetics.

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Conflict of interest statement

Financial & competing interests disclosure

This study was supported by the Canadian Institute for Cancer Research, Leukemia Lymphoma Society of Canada, Cancer Research Society and Charles Bruneau Foundation. Dana-Farber Cancer Institute ALL treatment protocols are supported by the National Cancer Institute/NIH grant 5 P01CA06848. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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