Basis for natural resistance to methotrexate in human acute non-lymphocytic leukemia.

Journal Article (Journal Article)

The basis of intrinsic resistance of blasts from patients with acute non-lymphocytic leukemia (ANLL) to methotrexate was studied. MTX polyglutamate formation was measured in blast cells from 19 patients with ANLL and in 7 pediatric patients with acute lymphocytic leukemia (ALL), after in vitro incubation for 24 h with 3H-methotrexate. There was no significant differences seen in the total amount of MTX plus polyglutamates measured between ANLL and ALL blasts, indicating that transport defects do not account for intrinsic MTX resistance in ANLL. However, there were significant differences between the amounts of long chain MTX polyglutamates found in ANLL cells as compared to ALL cells. Most, but not all, ANLL blasts were unable to form long chain polyglutamates. In as much as the level of MTX polyglutamates found in blast cells after MTX administration allows for retention of this drug, this property may explain, at least in part, the refractoriness of most patients with ANLL to methotrexate.

Full Text

Duke Authors

Cited Authors

  • Lin, JT; Tong, WP; Trippett, TM; Niedzwiecki, D; Tao, Y; Tan, C; Steinherz, P; Schweitzer, BI; Bertino, JR

Published Date

  • 1991

Published In

Volume / Issue

  • 15 / 12

Start / End Page

  • 1191 - 1196

PubMed ID

  • 1722550

International Standard Serial Number (ISSN)

  • 0145-2126

Digital Object Identifier (DOI)

  • 10.1016/0145-2126(91)90189-z


  • eng

Conference Location

  • England