Relationship between NUDT15 gene polymorphism and tolerance to treatment with 6-mercaptopurine in children with acute lymphoblastic leukemia
10.3760/cma.j.cn115356-20210507-00109
- VernacularTitle:NUDT15基因多态性与儿童急性淋巴细胞白血病6-巯基嘌呤治疗耐受性的关系
- Author:
Jing WANG
1
;
Xiaohuan WANG
;
Guoping HAO
;
Yanli CHENG
;
Haiyan LU
;
Taoli SUO
Author Information
1. 山西省儿童医院晋源院区血液科,太原 030025
- Keywords:
Leukemia, lymphoid;
Polymorphism, single nucleotide;
Gene, NUDT15;
Mercaptopurine;
Neutropenia
- From:
Journal of Leukemia & Lymphoma
2022;31(5):286-289
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the relationship between NUDT15 gene polymorphism and tolerance to treatment with 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL).Methods:Fifty-eight children diagnosed with ALL in Shanxi Children's Hospital from January 2019 to December 2020 were recruited. All of them were treated with CCLG-ALL2018 chemotherapy regimen and the bone marrow showed complete remission. They received 6-MP oral treatment during maintenance treatment. Single nucleotide polymorphism of NUDT15 gene was detected by real-time fluorescence quantitative polymerase chain reaction. The bone marrow suppression after 6-MP treatment and 6-MP tolerance dose in patients with different NUDT15 genotypes were analyzed.Results:Among 58 patients, 3 patients had NUDT15 TT genotype, 46 patients had CC genotype and 9 patients had TC genotype. During maintenance treatment with 6-MP, the differences in leukocyte count, hemoglobin and platelet count among the three groups of patients with different NUDT15 genotypes were statistically significant (all P < 0.05). Among 58 patients, 23 (39.66%) patients had varying degrees of neutropenia after medication, including 16 cases of NUDT15 CC genotype, 5 cases of TC genotype and 2 cases of TT genotype. There was a statistically significant difference in bone marrow suppression among the three groups ( H = 29.10, P < 0.05). The dosages of 6-MP used in patients with TT, CC and TC genotypes were (10.4±8.8) mg·m -2·d -1, (41.5±1.3) mg·m -2·d -1 and (36.7±2.4) mg·m -2·d -1, respectively, and the difference was statistically significant ( F = 16.95, P < 0.05). Conclusions:Children with different NUDT15 genotypes have different tolerance to 6-MP, and NUDT15 gene polymorphism is associated with 6-MP intolerance during maintenance treatment in children with ALL, which may affect the treatment of the disease.