MTHFR and acute lymphoblastic leukemia: Relations between clinical response and systematic toxicity after MTX treatment and gene variation in the folate metabolic pathway have been detected many times Most studies have focused on MTHFR C677T and RFC G80A and suggested that these polymorphisms contribute to MTX therapy-related toxicity or outcome of childhood ALL (Umerez et al., 2017, Tiwari et al., 2018).