Decreased polyglutamylation of methotrexate in acute lymphoblastic leukemia blasts in adults compared to children with this disease

Leukemia. 1993 Jul;7(7):1000-4.


We compared blast cells from adult and pediatric patients with untreated acute lymphoblastic leukemia (ALL) (as separated groups of T-lineage cell and B-lineage cell ALL) to determine if methotrexate (MTX) polyglutamate 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 total MTX and polyglutamates, especially long-chain MTX polyglutamates (glu3-6) than pediatric B-lineage cell ALL blasts. In view of the importance of polyglutamylation of MTX as a determinant of cytotoxicity of this drug, decreased formation of MTX polyglutamates is likely a contributing cause to the lower cure rate in adult ALL and T-lineage cell ALL as compared to childhood B-lineage cell ALL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Child
  • Drug Resistance
  • Humans
  • In Vitro Techniques
  • Methotrexate / metabolism*
  • Polyglutamic Acid / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Tumor Cells, Cultured


  • Polyglutamic Acid
  • Methotrexate