Patients with ARID5B SNP risk alleles were proven to have greater intracellular accumulation of MTX polyglutamates (MTXPGs), which mainly determine the cytotoxicity and antileukemic effects of MTX, especially in individuals with hyperdipoid B-ALL (Masson et al., 1996; Treviño et al., 2009), concomitant with the better response of B-ALL to MTX chemotherapy (Kager et al., 2005; Treviño et al., 2009; Xu et al., 2012). Here, ARID5B is linked to precursor B-cell acute lymphoblastic leukemia.