We herein describe novel risk loci for B-ALL at 9q21.31 (rs76925697, P = 2.11 × 10<sup>-8</sup>), for high-hyperdiploid ALL at 5q31.1 (rs886285, P = 1.56 × 10<sup>-8</sup>) and 6p21.31 (rs210143 in BAK1, P = 2.21 × 10<sup>-8</sup>), and ETV6-RUNX1 ALL at 17q21.32 (rs10853104 in IGF2BP1, P = 1.82 × 10<sup>-8</sup>).
Folylpolyglutamate synthetase (FPGS) activity was higher in B vs T lineage ALL (p<0.005), MTX influx and FPGS activity were higher in hyperdiploid vs non-hyperdiploid ALL (p<0.03), MTX influx and FPGS activity were lower in the t(12;21) (ETV6-RUNX1) subtype (p<0.05), and the ratio of FPGS to γ-glutamyl hydrolase (GGH) activity was lower in the t(1;19) (TCF3-PBX1) subtype (p<0.03) than other genetic subtypes.