Methotrexate polyglutamate synthesis in lymphoblasts from children with acute lymphoblastic leukemia

Lymphoblasts obtained from children at the time of diagnosis of acute lymphoblastic leukemia accumulated predominantly long-chain methotrexate polyglutamates containing 4-6 glutamyl residues when incubated with methotrexate in vitro. While methotrexate polyglutamates of these chain lengths are formed in other cells, they constitute only a minor proportion of polyglutamates in them. This extensive accumulation of long-chain methotrexate polyglutamates in lymphoblasts may explain in part the efficacy of methotrexate in the treatment of childhood acute lymphoblastic leukemia.