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

Erdem Göker, James T. Lin, Tanya Trippett, Yaroslav Elisseyeff, William P. Tong, Donna Niedzwiecki, Charlotte Tan, Peter Steinherz, Barry I. Schweitzer, Joseph R. Bertino

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1000-1004
Number of pages5
JournalLeukemia
Volume7
Issue number7
StatePublished - Jul 1993

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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