DECREASED POLYGLUTAMYLATION OF METHOTREXATE IN ACUTE LYMPHOBLASTIC-LEUKEMIA BLASTS IN ADULTS COMPARED TO CHILDREN WITH THIS DISEASE

We compared blast cells from adult and pediatric patients with untreat ed acute lymphoblastic leukemia (ALL) (as separated groups of T-lineag e cell and B-lineage cell ALL) to determine if methotrexate (MTX) poly glutamate formation in adult patients might be a contributing cause to the known difference in clinical outcome, since MTX is a key drug in chemotherapy regimens. Adult B-lineage cell ALL blasts and blasts from the patients with T-lineage cell ALL accumulated lower amounts of tot al MTX and polyglutamates, especially long-chain MTX polyglutamates (g lu3-6) than pediatric B-lineage cell ALL blasts. In view of the import ance of polyglutamylation of MTX as a determinant of cytotoxicity of t his drug, decreased formation of MTX polyglutamates is likely a contri buting cause to the lower cure rate in adult ALL and T-lineage cell AL L as compared to childhood B-lineage cell ALL.