PMID- 32372697
OWN - NLM
STAT- MEDLINE
DCOM- 20210426
LR  - 20210426
IS  - 1744-8042 (Electronic)
IS  - 1462-2416 (Print)
IS  - 1462-2416 (Linking)
VI  - 21
IP  - 8
DP  - 2020 Jun
TI  - HLA alleles associated with asparaginase hypersensitivity in childhood ALL: a 
      report from the DFCI Consortium.
PG  - 541-547
LID - 10.2217/pgs-2019-0195 [doi]
AB  - 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.
FAU - Gagne, Vincent
AU  - Gagne V
AD  - Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, University of 
      Montreal, Montreal, Quebec, H3T 1C5, Canada.
FAU - St-Onge, Pascal
AU  - St-Onge P
AD  - Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, University of 
      Montreal, Montreal, Quebec, H3T 1C5, Canada.
FAU - Beaulieu, Patrick
AU  - Beaulieu P
AD  - Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, University of 
      Montreal, Montreal, Quebec, H3T 1C5, Canada.
FAU - Laverdiere, Caroline
AU  - Laverdiere C
AD  - Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, University of 
      Montreal, Montreal, Quebec, H3T 1C5, Canada.
AD  - Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, 
      Quebec, H3T 1J4, Canada.
FAU - Leclerc, Jean-Marie
AU  - Leclerc JM
AD  - Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, University of 
      Montreal, Montreal, Quebec, H3T 1C5, Canada.
AD  - Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, 
      Quebec, H3T 1J4, Canada.
FAU - Tran, Thai H
AU  - Tran TH
AD  - Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, University of 
      Montreal, Montreal, Quebec, H3T 1C5, Canada.
AD  - Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, 
      Quebec, H3T 1J4, Canada.
FAU - Sallan, Stephen E
AU  - Sallan SE
AD  - Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, 
      USA.
AD  - Division of Hematology/Oncology, Children's Hospital, Boston, MA 02115, USA.
FAU - Neuberg, Donna
AU  - Neuberg D
AD  - Department of Biostatistics & Computational Biology, Dana-Farber Cancer 
      Institute, Boston, MA 02215, USA.
FAU - Silverman, Lewis B
AU  - Silverman LB
AD  - Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, 
      USA.
AD  - Division of Hematology/Oncology, Children's Hospital, Boston, MA 02115, USA.
FAU - Sinnett, Daniel
AU  - Sinnett D
AD  - Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, University of 
      Montreal, Montreal, Quebec, H3T 1C5, Canada.
AD  - Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, 
      Quebec, H3T 1J4, Canada.
FAU - Krajinovic, Maja
AU  - Krajinovic M
AD  - Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, University of 
      Montreal, Montreal, Quebec, H3T 1C5, Canada.
AD  - Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, 
      Quebec, H3T 1J4, Canada.
AD  - Department of Pharmacology & physiology, Faculty of Medicine, University of 
      Montreal, Montreal, Quebec, H3T 1J4, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200506
PL  - England
TA  - Pharmacogenomics
JT  - Pharmacogenomics
JID - 100897350
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DRB1 Chains)
RN  - EC 3.5.1.1 (Asparaginase)
SB  - IM
MH  - Asparaginase/*metabolism
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Female
MH  - HLA-DQ alpha-Chains/*genetics
MH  - HLA-DQ beta-Chains/*genetics
MH  - HLA-DRB1 Chains/*genetics
MH  - Humans
MH  - Male
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*enzymology/epidemiology/*genetics
MH  - Quebec/epidemiology
PMC - PMC7299187
OTO - NOTNLM
OT  - SNP
OT  - acute lymphoblastic leukemia
OT  - asparaginase
OT  - asparaginase hypersensitivity
OT  - human leukocyte antigen
OT  - pharmacogenetics
COIS- 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.
EDAT- 2020/05/07 06:00
MHDA- 2021/04/27 06:00
PMCR- 2021/03/01
CRDT- 2020/05/07 06:00
PHST- 2020/05/07 06:00 [pubmed]
PHST- 2021/04/27 06:00 [medline]
PHST- 2020/05/07 06:00 [entrez]
PHST- 2021/03/01 00:00 [pmc-release]
AID - 10.2217/pgs-2019-0195 [doi]
PST - ppublish
SO  - Pharmacogenomics. 2020 Jun;21(8):541-547. doi: 10.2217/pgs-2019-0195. Epub 2020 
      May 6.