Chemosensitivity to triazene compounds and O6-alkylguanine-DNA alkyltransferase levels: studies with blasts of leukaemic patients.
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-alkylguanine-DNA alkyltransferase (OGAT).


METHODS
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.
D'Atri
S
S
Istituto Dermopatico dell'Immacolata (IDI), University of Rome, Tor Vergata, Italy.
Piccioni
D
D
Castellano
A
A
Tuorto
V
V
Franchi
A
A
Lu
K
K
Christiansen
N
N
Frankel
S
S
Rustum
Y M
YM
Papa
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003561:Cytarabine / Q000627:therapeutic use; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008780:Methyltransferases / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010641:Phenotype; D010865:Pilot Projects; D000077204:Temozolomide
D000970:Antineoplastic Agents; D003561:Cytarabine; D003606:Dacarbazine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide