Journal of clinical pharmacy and therapeutics · 2020
Methylation analysis of the SLC19A1 promoter region in Chinese children with acute lymphoblastic leukaemia.
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Wang Shu-Mei, Li Miao, Wu Wan-Shui, Sun Lu-Lu, Yan Dan
Аннотация
WHAT IS KNOWN AND OBJECTIVE: Reduced folate carrier 1 (RFC1), which is encoded by the human solute carrier family 19 member 1 (SLC19A1) gene, plays an essential role in the cellular uptake of methotrexate (MTX). RFC1 expression is regulated by genetic variations and epigenetic modifications. The aim of the present study was to investigate the methylation status of the SLC19A1 promoter in peripheral blood and its association with MTX levels and toxicities in children with acute lymphoblastic leukaemia (ALL).
METHODS: Serum MTX concentrations were measured using a fluorescence polarization immunoassay. Methylation quantification for SLC19A1 promoter region #17 was performed by Sequenom MassARRAY in 52 paediatric ALL patients.
RESULTS AND DISCUSSION: Overall, the investigated region of the SLC19A1 promoter was in a hypermethylated state. No significant associations were detected between the methylation levels of six CpG units in the SLC19A1 promoter region #17 and clinical parameters of patients with ALL, including sex, age, immunotype and risk stratification. The methylation level of CpG_10 showed a significant positive correlation with MTX 24 hours after the initiation of infusion. No significant differences in the methylation levels of six CpG units were observed between patients with and without MTX toxicities. Due to the small sample size of this study, there was a high chance of false-positive results. A large-scale study would be required to confirm these preliminary results.
WHAT IS NEW AND CONCLUSION: Our preliminary results suggested the hypermethylated status of the SLC19A1 promoter in children with ALL. The methylation levels of the SLC19A1 promoter might affect MTX exposure. These findings have implications for the mechanisms underlying the variability of MTX responses in childhood ALL.
METHODS: Serum MTX concentrations were measured using a fluorescence polarization immunoassay. Methylation quantification for SLC19A1 promoter region #17 was performed by Sequenom MassARRAY in 52 paediatric ALL patients.
RESULTS AND DISCUSSION: Overall, the investigated region of the SLC19A1 promoter was in a hypermethylated state. No significant associations were detected between the methylation levels of six CpG units in the SLC19A1 promoter region #17 and clinical parameters of patients with ALL, including sex, age, immunotype and risk stratification. The methylation level of CpG_10 showed a significant positive correlation with MTX 24 hours after the initiation of infusion. No significant differences in the methylation levels of six CpG units were observed between patients with and without MTX toxicities. Due to the small sample size of this study, there was a high chance of false-positive results. A large-scale study would be required to confirm these preliminary results.
WHAT IS NEW AND CONCLUSION: Our preliminary results suggested the hypermethylated status of the SLC19A1 promoter in children with ALL. The methylation levels of the SLC19A1 promoter might affect MTX exposure. These findings have implications for the mechanisms underlying the variability of MTX responses in childhood ALL.