Influence of the ABCC2 polymorphism -24C>T on the plasma concentration and toxicity of high-dose methotrexate in childhood acute lymphoblastic leukemia
Objective:To identify the influence of -24C>T ABCC2 on the variability of high-dose methotrexate (MTX) plasma concentration and toxicity in pediatric acute lymphocytic leukemia (ALL) patients. Methods: A total of 132 healthy children and 39 pediatric ALL patients were included in the study. All patients were treated according to the ALL-BFM-2005 protocol. After 3 cycles of treatment with 3000-5000 mg MTX/m2 (body surface area), associations among ABCC2 polymorphism, MTX plasma concentration, and incidence of side effects were assessed, variation of the ABCC2 gene was analyzed by sequencing. Results: The frequency of the T allele in ALL was 0.35, indicating a strong association with ALL (p = 0.041,OR =4.5, 95％CI=1.8-7.6). The variant was highly associated with high concentrations of methotrexate (p = 0.017,OR = 2.17, 95％ CI= 1.24-3.52). The T allele was a higher risk factor for leukemia(p = 0.045,OR = 1.97,95％ CI = 1.05-3.14). Conclusion: The -24C>T variant could change the function of ABCC2, then can change the elimination of methorexate. This variant may be used as a predictive marker for the risk of delayed methotrexate elimination.
gene polymorphism ATP-binding cassette sub-family C member 2 methotrexate elimination toxicity childhood acute lymphoblastic leukemia
Yan Liu Jian Zhang Qi Sheng You Yin Xiao-Tong Lu Fang Wang Huai-Ping Tian A-Jing Xu Shu-Hong Bu Li-xia Li
Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, Department of Pediatric Hematology /Oncology, Xinhua Hospital, Shanghai Jiaotong University School o department of neurology, Changzheng Hospital Affiliated to Secengd Military Medical University, Shan
国内会议
烟台
英文
1-19
1900-01-01（万方平台首次上网日期，不代表论文的发表时间）