Pharmacogenetics of acute lymphoblastic leukemia

Our research focused on investigating the involvement of polymorphisms (C677T and A1298C) of the MTHFR gene in the pharmacogenetics of acute lymphoblastic leukemia (ALL), particularly with high-dose methotrexate (MTX-HD). Despite its proven clinical efficacy, the latter can cause severe toxicity. 41 young children followed for ALL were collected. Genotyping of the two variants was correlated with therapeutic response and pharmacological assays (MTX and homocysteine) While MTHFR C677T is a good marker of MTX-HD toxicity, A1298C is not. Nevertheless, no correlation between the C677T variant and pharmacokinetic parameters during MTX-HD administrationIn conclusion, despite the debate concerning the existence of a pharmacogenetic marker for the use of MTX in clinical practice, the C677T polymorphism of the MTHFR shows promising results.