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

  

Authors:	Lin, J. T.; Tong, W. P.; Trippett, T. M.; Niedzwiecki, D.; Tao, Y.; Tan, C.; Steinherz, P.; Schweitzer, B. I.; Bertino, J. R.
Article Title:	Basis for natural resistance to methotrexate in human acute non-lymphocytic leukemia
Abstract:	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 were 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. © 1991.
Keywords:	adolescent; adult; child; clinical article; controlled study; aged; child, preschool; human cell; comparative study; methotrexate; bone marrow; drug resistance; tumor cells, cultured; drug retention; infant; acute lymphocytic leukemia; dihydrofolate reductase; tetrahydrofolate dehydrogenase; cell level; blast cell; middle age; acute nonlymphocytic leukemia; polyglutamic acid; leukemia, lymphocytic, acute, l1; leukemia, nonlymphocytic, acute; human; male; female; priority journal; article; support, non-u.s. gov't; methotrexate polyglutamate; acute non-lymphocytic leukemia; natural resistance
Journal Title:	Leukemia Research
Volume:	15
Issue:	12
ISSN:	0145-2126
Publisher:	Elsevier Ltd
Date Published:	1991-01-01
Start Page:	1191
End Page:	1196
Language:	English
DOI:	10.1016/0145-2126(91)90189-z
PUBMED:	1722550
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0026342183&doi=10.1016%2f0145-2126%2891%2990189-Z&partnerID=40&md5=7604b0ffa5b57b6e286f54e8f16f0892
Notes:	Source: Scopus

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