期刊
PEDIATRIC HEMATOLOGY AND ONCOLOGY
卷 39, 期 3, 页码 254-266出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/08880018.2021.1973628
关键词
Acute lymphoblastic leukemia; genetics predictors; 6-mercaptopurine intolerance; NUDT15; pediatrics
资金
- Private Donation 'Mr. and Mrs. Wu Fund'
The study evaluated the association of common variants of ABCC4, ITPA, NUDT15, and TPMT with 6-MP dose intensity and toxicity in pediatric ALL patients. Results showed significant associations between NUDT15 and ABCC4, ITPA variants with 6-MP dose intensity and intolerance, recommending pharmacogenetic screening for ALL patients to avoid 6-MP induced toxicity.
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
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