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Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008

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Harvard

Højfeldt, SG, Wolthers, BO, Tulstrup, M, Abrahamsson, J, Gupta, R, Harila-Saari, A, Heyman, M, Henriksen, LT, Jónsson, ÒG, Lähteenmäki, PM, Lund, B, Pruunsild, K, Vaitkeviciene, G, Schmiegelow, K, Albertsen, BK & Nordic Society of Paediatric Haematology Oncology (NOPHO) group 2019, 'Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008' British Journal of Haematology, bind 184, nr. 3, s. 405-417. https://doi.org/10.1111/bjh.15660

APA

Højfeldt, S. G., Wolthers, B. O., Tulstrup, M., Abrahamsson, J., Gupta, R., Harila-Saari, A., ... Nordic Society of Paediatric Haematology Oncology (NOPHO) group (2019). Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008. British Journal of Haematology, 184(3), 405-417. https://doi.org/10.1111/bjh.15660

CBE

Højfeldt SG, Wolthers BO, Tulstrup M, Abrahamsson J, Gupta R, Harila-Saari A, Heyman M, Henriksen LT, Jónsson ÒG, Lähteenmäki PM, Lund B, Pruunsild K, Vaitkeviciene G, Schmiegelow K, Albertsen BK, Nordic Society of Paediatric Haematology Oncology (NOPHO) group. 2019. Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008. British Journal of Haematology. 184(3):405-417. https://doi.org/10.1111/bjh.15660

MLA

Vancouver

Author

Højfeldt, Sofie G ; Wolthers, Benjamin O ; Tulstrup, Morten ; Abrahamsson, Jonas ; Gupta, Ramneek ; Harila-Saari, Arja ; Heyman, Mats ; Henriksen, Louise T ; Jónsson, Òlafur G ; Lähteenmäki, Päivi M ; Lund, Bendik ; Pruunsild, Kaie ; Vaitkeviciene, Goda ; Schmiegelow, Kjeld ; Albertsen, Birgitte K ; Nordic Society of Paediatric Haematology Oncology (NOPHO) group. / Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008. I: British Journal of Haematology. 2019 ; Bind 184, Nr. 3. s. 405-417.

Bibtex

@article{6ec28f3db48a4be8998ada150bb517f7,
title = "Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008",
abstract = "Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8{\%} (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10-8 ). We further identified two signals on chromosome 6 in relation to HLA-DQA1 (P = 9·37 × 10-6 ) and TAP2 (P = 1·59 × 10-5 ). This study associated variants in CNOT3 and in the human leucocyte antigen (HLA) region with PEG-asparaginase hypersensitivity, suggesting that not only genetic variations in the HLA region, but also regulation of these genes are of importance in the biology of this toxicity. Furthermore, our study emphasizes the importance of using asparaginase enzyme activity measurements to identify PEG-asparaginase hypersensitivity.",
keywords = "ATP Binding Cassette Transporter, Subfamily B, Member 3/genetics, Adolescent, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Asparaginase/administration & dosage, Child, Child, Preschool, Chromosomes, Human, Pair 19/genetics, Chromosomes, Human, Pair 6/genetics, Drug Hypersensitivity/genetics, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, HLA-DQ Antigens/genetics, Humans, Infant, Male, Neoplasm Proteins/genetics, Polyethylene Glycols/administration & dosage, Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, Transcription Factors/genetics",
author = "H{\o}jfeldt, {Sofie G} and Wolthers, {Benjamin O} and Morten Tulstrup and Jonas Abrahamsson and Ramneek Gupta and Arja Harila-Saari and Mats Heyman and Henriksen, {Louise T} and J{\'o}nsson, {{\`O}lafur G} and L{\"a}hteenm{\"a}ki, {P{\"a}ivi M} and Bendik Lund and Kaie Pruunsild and Goda Vaitkeviciene and Kjeld Schmiegelow and Albertsen, {Birgitte K} and {Nordic Society of Paediatric Haematology Oncology (NOPHO) group}",
note = "{\circledC} 2018 British Society for Haematology and John Wiley & Sons Ltd.",
year = "2019",
doi = "10.1111/bjh.15660",
language = "English",
volume = "184",
pages = "405--417",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",

}

RIS

TY - JOUR

T1 - Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008

AU - Højfeldt, Sofie G

AU - Wolthers, Benjamin O

AU - Tulstrup, Morten

AU - Abrahamsson, Jonas

AU - Gupta, Ramneek

AU - Harila-Saari, Arja

AU - Heyman, Mats

AU - Henriksen, Louise T

AU - Jónsson, Òlafur G

AU - Lähteenmäki, Päivi M

AU - Lund, Bendik

AU - Pruunsild, Kaie

AU - Vaitkeviciene, Goda

AU - Schmiegelow, Kjeld

AU - Albertsen, Birgitte K

AU - Nordic Society of Paediatric Haematology Oncology (NOPHO) group

N1 - © 2018 British Society for Haematology and John Wiley & Sons Ltd.

PY - 2019

Y1 - 2019

N2 - Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10-8 ). We further identified two signals on chromosome 6 in relation to HLA-DQA1 (P = 9·37 × 10-6 ) and TAP2 (P = 1·59 × 10-5 ). This study associated variants in CNOT3 and in the human leucocyte antigen (HLA) region with PEG-asparaginase hypersensitivity, suggesting that not only genetic variations in the HLA region, but also regulation of these genes are of importance in the biology of this toxicity. Furthermore, our study emphasizes the importance of using asparaginase enzyme activity measurements to identify PEG-asparaginase hypersensitivity.

AB - Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10-8 ). We further identified two signals on chromosome 6 in relation to HLA-DQA1 (P = 9·37 × 10-6 ) and TAP2 (P = 1·59 × 10-5 ). This study associated variants in CNOT3 and in the human leucocyte antigen (HLA) region with PEG-asparaginase hypersensitivity, suggesting that not only genetic variations in the HLA region, but also regulation of these genes are of importance in the biology of this toxicity. Furthermore, our study emphasizes the importance of using asparaginase enzyme activity measurements to identify PEG-asparaginase hypersensitivity.

KW - ATP Binding Cassette Transporter, Subfamily B, Member 3/genetics

KW - Adolescent

KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage

KW - Asparaginase/administration & dosage

KW - Child

KW - Child, Preschool

KW - Chromosomes, Human, Pair 19/genetics

KW - Chromosomes, Human, Pair 6/genetics

KW - Drug Hypersensitivity/genetics

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - HLA-DQ Antigens/genetics

KW - Humans

KW - Infant

KW - Male

KW - Neoplasm Proteins/genetics

KW - Polyethylene Glycols/administration & dosage

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy

KW - Transcription Factors/genetics

U2 - 10.1111/bjh.15660

DO - 10.1111/bjh.15660

M3 - Journal article

VL - 184

SP - 405

EP - 417

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 3

ER -

ID: 59083781