دورية أكاديمية
ABCC4 , ITPA , NUDT15 , TPMT and their interaction as genetic predictors of 6-mercaptopurine intolerance in chinese patients with acute lymphoblastic leukemia.
| العنوان: | ABCC4 , ITPA , NUDT15 , TPMT and their interaction as genetic predictors of 6-mercaptopurine intolerance in chinese patients with acute lymphoblastic leukemia. |
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| المؤلفون: | Fan POL; Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China., Leung KT; Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.; Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China., Chan KYY; Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China., Leung AWK; Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.; Department of Paediatrics & Adolescent Medicine, The Hong Kong Children's Hospital, Hong Kong SAR, China., Lam GKS; Department of Paediatrics & Adolescent Medicine, The Hong Kong Children's Hospital, Hong Kong SAR, China., Chow TTW; Department of Paediatrics & Adolescent Medicine, The Hong Kong Children's Hospital, Hong Kong SAR, China., Cheng FWT; Department of Paediatrics & Adolescent Medicine, The Hong Kong Children's Hospital, Hong Kong SAR, China., Yuen LYP; Department of Pathology, The Hong Kong Children's Hospital, Hong Kong SAR, China., Moriyama T; Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA., Yang JJ; Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA., Li CK; Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.; Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China.; Department of Paediatrics & Adolescent Medicine, The Hong Kong Children's Hospital, Hong Kong SAR, China. |
| المصدر: | Pediatric hematology and oncology [Pediatr Hematol Oncol] 2022 Apr; Vol. 39 (3), pp. 254-266. Date of Electronic Publication: 2021 Oct 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 8700164 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-0669 (Electronic) Linking ISSN: 08880018 NLM ISO Abbreviation: Pediatr Hematol Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2006- : London : Informa Healthcare Original Publication: Washington, DC : Hemisphere Pub. Corp., c1986- |
| مواضيع طبية MeSH: | Antimetabolites, Antineoplastic*/adverse effects , Antimetabolites, Antineoplastic*/therapeutic use , Mercaptopurine*/adverse effects , Mercaptopurine*/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma*/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma*/genetics, Child ; China ; Humans ; Methyltransferases/genetics ; Multidrug Resistance-Associated Proteins/genetics ; Pyrophosphatases/genetics |
| مستخلص: | Inter-individual variance in 6-mercaptopurine (6-MP) dose intensity is common in patients with acute lymphoblastic leukemia (ALL). We aimed to evaluate the association of common variants of ABCC4 , ITPA , NUDT15 , and TPMT with 6-MP dose intensity and toxicity in pediatric ALL patients. In this cohort, 13.8% of patients were intolerant to 6-MP with actual dosage less than 50% of scheduled dose. Twenty percent of patients were found to be heterozygous or homozygous mutated with NUDT15 . NUDT15 c.415C > T and the genotype-predicted NUDT15 activity were significantly associated with 6-MP intolerance. TPMT *3C variants were not common in this cohort (2.8%). NUDT15 polymorphisms and genotype predicted NUDT15 activity were significantly associated with 6-MP dose intensity and leukopenia episodes. Combination of ABCC4 and ITPA variants ( ABCC4 c.912G > T and ITPA c.94C > A) also showed significant positive association with 6-MP intolerance in Chinese children with ALL. Further study on pharmacogenetic screening for ALL patients to avoid 6-MP induced toxicity is recommended.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1973628. |
| فهرسة مساهمة: | Keywords: NUDT15; 6-mercaptopurine intolerance; Acute lymphoblastic leukemia; genetics predictors; pediatrics |
| المشرفين على المادة: | 0 (ABCC4 protein, human) 0 (Antimetabolites, Antineoplastic) 0 (Multidrug Resistance-Associated Proteins) E7WED276I5 (Mercaptopurine) EC 2.1.1.- (Methyltransferases) EC 2.1.1.67 (TPMT protein, human) EC 2.6.1.- (NUDT15 protein, human) EC 3.6.1.- (Pyrophosphatases) EC 3.6.1.9 (ITPA protein, human) |
| تواريخ الأحداث: | Date Created: 20211019 Date Completed: 20220401 Latest Revision: 20220531 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1080/08880018.2021.1973628 |
| PMID: | 34665987 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1521-0669 |
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| DOI: | 10.1080/08880018.2021.1973628 |