Collateral sensitivity to azidothymidine in methotrexate resistant human leukemia cells

H. Miyachi, L. Jiao, L. C. Sowers, K. J. Scanlon

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Resistance to methotrexate (MTX) is a well established clinical problem and strategies to circumvent this would obviously be beneficial. The human leukemia cell line, CCRF-CEM, was grown in folinic acid to study MTX resistance-reflecting more in vivo conditions. A 15.8-fold resistant subline, CEM/MTX, was evolved by stepwise increases in MTX exposure. The MTX resistant cell line exhibited both increased dihydrofolate reductase (DHFR) activity due to gene amplification as well as impaired MTX uptake. An additional mechanism of resistance to MTX was a 2-fold increase in thymidine kinase (TK). As a result of this increased TK activity, the CEM/MTX cells were collaterally sensitive to the nucleoside analogue, azidothymidine (AZT). CEM cells resistant to MTX possess properties that can be exploited by AZT and these studies may have clinical implications.

Original languageEnglish (US)
Pages (from-to)17-21
Number of pages5
JournalIn Vivo
Volume6
Issue number1
StatePublished - Jan 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

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