Chemosensitivity to triazene compounds and O6-alkylguanine-DNA alkyltransferase levels: Studies with blasts of leukaemic patients

S. D'Atri, D. Piccioni, A. Castellano, V. Tuorto, A. Franchi, N. Christiansen, S. Frankel, Y. M. Rustum, G. Papa, F. Mandeli, E. Bonmassar

Research output: Contribution to journalArticle

Abstract

Background: A clinical pilot study performed by our group showed that dacarbazine can induce a marked reduction of blast cells in patients with acute myelogenous leukaemia (AML). Leukaemic blasts (LB) from responsive patients showed low levels of O6-allcylguanine-DNA alkyltransferase (OGAT). Design: An in vitro study was performed to evaluate OGAT levels and sensitivity to temozolomide (a triazene compound that spontaneously decomposes into the active metabolite of dacarbazine) in a relatively large number of LB samples. Results: OGAT levels varied widely among the LB of different patients, with a mean value higher in acute lymphoblastic leukaemias than in AML. About 25% of LB obtained from patients with AML showed low OGAT activity, in the range corresponding to that observed in leukaemic patients responsive to dacarbazine in vivo. A reasonable inverse correlation was found between OGAT levels and LB sensitivity to temozolomide. Conclusions: Triazenes could have a therapeutic potential in human leukaemias. Moreover, OGAT determination could provide rapid and reliable information about a patient's susceptibility to these antitumor agents.

Original languageEnglish
Pages (from-to)389-393
Number of pages5
JournalAnnals of Oncology
Volume6
Issue number4
Publication statusPublished - 1995

Keywords

  • Alkyltransferase
  • Chemosensitivity
  • Leukaemia
  • Triazenes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Hematology

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    D'Atri, S., Piccioni, D., Castellano, A., Tuorto, V., Franchi, A., Christiansen, N., Frankel, S., Rustum, Y. M., Papa, G., Mandeli, F., & Bonmassar, E. (1995). Chemosensitivity to triazene compounds and O6-alkylguanine-DNA alkyltransferase levels: Studies with blasts of leukaemic patients. Annals of Oncology, 6(4), 389-393.