Effects of SCT genetic polymorphisms on methotrexate concentrations and toxicities in Chinese children with acute lymphoblastic leukemia.

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia & Lymphoma Pub Date : 2025-01-11 DOI:10.1080/10428194.2025.2451059

Miao Li, Dan-Qi Zhao, Xiao-Yan Kong, Shu-Mei Wang

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Abstract

Solute carrier (SLC) transporters play a crucial role in facilitating the cellular uptake of various anticancer drugs, such as methotrexate (MTX). This study aimed to analyze the impact of nonsynonymous single nucleotide polymorphisms (SNPs) in SLC19A1, SLCO1B1, and SLCO1B3 on MTX exposure, toxicities, and prognosis in 148 patients with acute lymphoblastic leukemia (ALL). The SLCO1B3 rs7311358 polymorphism was significantly associated with the median dose-normalized MTX concentrations at 24 h (p < .05). There were significant differences in the proportions of patients with serum MTX levels >40 µmol/L at 24 h among SLC19A1 rs1051266 GG, GA, and AA genotype carriers (29.0, 24.7, and 6.2%, respectively, p < .05). The SLC19A1 rs1051266 G > A polymorphism also displayed significant associations with hematological (p < .05) and hepatic toxicities (p < .01). Our findings indicate that the analysis of SNPs in solute carrier transporters (SCTs) could offer valuable insights into the interpatient variability of MTX pharmacokinetics and toxicities in ALL children.

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SCT基因多态性对中国急性淋巴细胞白血病儿童甲氨蝶呤浓度和毒性的影响。

溶质载体（SLC）转运体在促进细胞摄取各种抗癌药物（如甲氨蝶呤（MTX））中起着至关重要的作用。本研究旨在分析148例急性淋巴细胞白血病（ALL）患者中SLC19A1、SLCO1B1和SLCO1B3非同义单核苷酸多态性（snp）对MTX暴露、毒性和预后的影响。SLCO1B3 rs7311358多态性与SLC19A1 rs1051266 GG、GA和AA基因型携带者24 h时MTX中位剂量标准化浓度（p 40µmol/L）显著相关（分别为29.0%、24.7%和6.2%），p SLC19A1 rs1051266 G > A多态性也与血液学(p p p

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来源期刊

Leukemia & Lymphoma 医学-血液学

CiteScore

4.10

自引率

3.80%

发文量

384

审稿时长

1.8 months

期刊介绍： Leukemia & Lymphoma in its fourth decade continues to provide an international forum for publication of high quality clinical, translational, and basic science research, and original observations relating to all aspects of hematological malignancies. The scope ranges from clinical and clinico-pathological investigations to fundamental research in disease biology, mechanisms of action of novel agents, development of combination chemotherapy, pharmacology and pharmacogenomics as well as ethics and epidemiology. Submissions of unique clinical observations or confirmatory studies are considered and published as Letters to the Editor