Correlation between methylation level of the SLC19A1 promoter region and methotrexate metabolism in adult acute lymphoblastic leukemia

Pharmacogenomics. 2023 Apr;24(5):261-268. doi: 10.2217/pgs-2022-0169. Epub 2023 Mar 31.

Abstract

Aims: To analyze the methylation level in the promoter region of SLC19A1 in adult acute lymphoblastic leukemia (ALL) patients, and explore the relationship between methotrexate (MTX) drug metabolism and SLC19A1 methylation. Methods: The methylation levels of the SLC19A1 promoter region in 52 adult ALL patients who received high-dose MTX chemotherapy were retrospectively analyzed in combination with clinical indicators and plasma MTX concentration. Results: Methylation levels of 17 CpG units were differently correlated with clinical parameters of ALL patients including gender, age, immunophenotype and Philadelphia chromosome status. Patients with delayed MTX drug excretion had higher methylation levels in the SLC19A1 promoter region. Conclusion: The methylation may affect the MTX plasma level and adverse reactions, which may predict patients at risk of adverse reactions after high-dose MTX therapy.

Keywords: SLC19A1; acute lymphoblastic leukemia; adult; high-dose MTX; methylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimetabolites, Antineoplastic / adverse effects
  • Humans
  • Methotrexate* / adverse effects
  • Methylation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Promoter Regions, Genetic / genetics
  • Reduced Folate Carrier Protein / genetics
  • Retrospective Studies

Substances

  • Methotrexate
  • Antimetabolites, Antineoplastic
  • SLC19A1 protein, human
  • Reduced Folate Carrier Protein