دورية أكاديمية
HLA-DRB1*07:01–HLA-DQA1*02:01–HLA-DQB1*02:02 haplotype is associated with a high risk of asparaginase hypersensitivity in acute lymphoblastic leukemia
| العنوان: | HLA-DRB1*07:01–HLA-DQA1*02:01–HLA-DQB1*02:02 haplotype is associated with a high risk of asparaginase hypersensitivity in acute lymphoblastic leukemia |
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| المؤلفون: | Nóra Kutszegi, Xiaoqing Yang, András Gézsi, Géza Schermann, Dániel J. Erdélyi, Ágnes F. Semsei, Krisztina M. Gábor, Judit C. Sági, Gábor T. Kovács, András Falus, Hongyun Zhang, Csaba Szalai |
| المصدر: | Haematologica, Vol 102, Iss 9 (2017) |
| بيانات النشر: | Ferrata Storti Foundation, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | Hypersensitivity reactions are the most frequent dose-limiting adverse reactions to Escherichia coli-derived asparaginase in pediatric acute lymphoblastic leukemia (ALL) patients. The aim of the present study was to identify associations between sequence-based Human Leukocyte Antigen Class II region alleles and asparaginase hypersensitivity in a Hungarian ALL population. Four-digit typing of HLA-DRB1 and HLA-DQB1 loci was performed in 359 pediatric ALL patients by using next-generation sequencing method. Based on genotypic data of the two loci, haplotype reconstruction was carried out. In order to investigate the possible role of the HLA-DQ complex, the HLA-DQA1 alleles were also inferred. Multivariate logistic regression analysis and a Bayesian network-based approach were applied to identify relevant genetic risk factors of asparaginase hypersensitivity. Patients with HLA-DRB1*07:01 and HLA-DQB1*02:02 alleles had significantly higher risk of developing asparaginase hypersensitivity compared to non-carriers [P=4.56×10−5; OR=2.86 (1.73–4.75) and P=1.85×10−4; OR=2.99 (1.68–5.31); n=359, respectively]. After haplotype reconstruction, the HLA-DRB1*07:01-HLA-DQB1*02:02 haplotype was associated with an increased risk. After inferring the HLA-DQA1 alleles the HLA-DRB1*07:01–HLA-DQA1*02:01–HLA-DQB1*02:02 haplotype was associated with the highest risk of asparaginase hypersensitivity [P=1.22×10−5; OR=5.00 (2.43–10.29); n=257]. Significantly fewer T-cell ALL patients carried the HLA-DQB1*02:02 allele and the associated haplotype than did pre-B-cell ALL patients (6.5%; vs. 19.2%, respectively; P=0.047). In conclusion, we identified a haplotype in the Human Leukocyte Antigen Class II region associated with a higher risk of asparaginase hypersensitivity. Our results confirm that variations in HLA-D region might influence the development of asparaginase hypersensitivity. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0390-6078 1592-8721 |
| Relation: | https://haematologica.org/article/view/8193; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721 |
| DOI: | 10.3324/haematol.2017.168211 |
| URL الوصول: | https://doaj.org/article/82087caef2774188b08a13c775c459b3 |
| رقم الأكسشن: | edsdoj.82087caef2774188b08a13c775c459b3 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 03906078 15928721 |
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| DOI: | 10.3324/haematol.2017.168211 |