CHEMOSENSITIVITY TO TRIAZENE COMPOUNDS AND O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE LEVELS - STUDIES WITH BLASTS OF LEUKEMIC PATIENTS

Background: A clinical pilot study performed by our group showed that dacarbazine can induce a marked reduction of blast cells in patients w ith acute myelogenous leukaemia (AML). Leukaemic blasts (LB) from resp onsive patients showed low levels of O-6-alkylguanine-DNA alkyltransfe rase (OGAT). Design: An in vitro study was performed to evaluate OGAT levels and sensitivity to temozolomide (a triazene compound that spont aneously decomposes into the active metabolite of dacarbazine) in a re latively large number of LB samples. Results: OGAT levels varied widel y among the LB of different patients, with a mean value higher in acut e 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 v ivo. A reasonable inverse correlation was found between OGAT levels an d LB sensitivity to temozolomide. Conclusions: Triazenes could have a therapeutic potential in human leukaemias. Moreover, OGAT determinatio n could provide rapid and reliable information about a patient's susce ptibility to these antitumor agents.