Abstract
MTHFR 677C>T and ABCB1 3435 C>T predicted the risk of delayed MTX clearance during HD-MTX treatment in children with ALL. Serum L-phenylalanine levels were significantly elevated after HD-MTX treatment in children with the MTHFR 677C>T mutation gene. This study was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2000035264; registration: 2020/08/05; https://www.chictr.org.cn/ ). • MTX-related genes play an important role in MTX pharmacokinetics and toxicity, but results from different studies are inconsistent and the mechanisms involved are not clear. • Characteristics, prognosis, polymorphisms of MTX-related genes, and metabolite changes were comprehensively evaluated in children treated with HD-MTX chemotherapy. • Analysis revealed that both heterozygous and pure mutations in MTHFR 677C>T resulted in a significantly increased risk of delayed MTX clearance, and that L-phenylalanine has the potential to serve as a predictive marker for the metabolic effects of the MTHFR 677C>T polymorphism.
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