Assessment of PTT 119 activity on acute nonlymphoblastic leukemia cells by [3H]-thymidine uptake inhibition and cluster analysis.
PTT 119, a new antineoplastic agent, was demonstrated to have antileukemic activity on murine and human cell lines. In this study we assessed the effect of this drug, at concentrations ranging from 100 ng/ml to 10 micrograms/ml, on fresh human leukemic cells from 12 patients affected by ANLL, evaluating the impairment of DNA synthesis in terms of [3H]-thymidine uptake inhibition. Most leukemic cell populations appeared to be responsive to the drug in a dose-related fashion. By cluster analysis, it was possible to discriminate subsets of samples according to PTT 119 sensitivity, and to investigate cross resistance with cytosine arabinoside and daunorubicin. This preclinical study indicates that PTT 119 may deserve applications in the treatment of acute nonlymphoblastic leukemia patients.
Dal Pozzo
O
O
U.O. Ematologia, USL 10/D, Università, Firenze, Italy.
Santini
V
V
Saccardi
R
R
Bernabei
P A
PA
Rossi Ferrini
P
P
D000754:Anemia, Refractory, with Excess of Blasts / Q000473:pathology; D016000:Cluster Analysis; D003561:Cytarabine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D009588:Nitrogen Mustard Compounds; D003561:Cytarabine; C038259:ambamustine; D013936:Thymidine; D003630:Daunorubicin