Methotrexate is particularly useful for treating this subtype of ALL, and the disease response is influenced by the intracellular accumulation of active methotrexate polyglutamate metabolites (MTXPGs), which is higher in hyperdiploid ALL than in ETV6/RUNX1 ALL, TCF3/PBX1 ALL, or T-ALL [24,25,26]. This evidence concerns the gene RUNX1 and acute lymphoblastic leukemia.