Apoptosis induction with purine analogs on freshly isolated chronic myeloid leukemia cells.

ing the month preceding the trial were selected for this study. Mononuclear cells from bone marrow samples were obtained after centrifugation of the cell suspension over a Ficoll/Hypaque gradient. The following mean percentages were observed in the mononuclear fraction of the samples: lymphocytes 30%, monocytes 20%, myelocytes 20%, metamyelocytes 15%, promyelocytes 10%, and blast cells 5%. FLU was purchased from Inveresk Clinical Research (Edinburgh, Scotland) and was used at a final concentration of 5 mg/mL. 2-CdA and pentostatin were a gift from Dr. V.L. Narayanan of the Drug Synthesis and Chemistry Branch of the National Cancer Institute (Bethesda, MD), and were used at a final concentration of 30 µmol/L and 5 mM, respectively. a-IFN (provided by Hoffman-La Roche, Basel, Switzerland) was tested at a final concentration of 100 U/mL. The combinations evaluated were the following: FLU (5 µg/mL) plus 2-CdA (30 µmol/L), FLU (5 µg/mL) plus pentostatin (5 µM), FLU (5 µg/mL) plus a-IFN (100 U/mL); 2-CdA (30 µmol/L) plus a-IFN (100 U/mL); pentostatin (5 µM) plus a-IFN (100 U/mL). The tumor cells were harvested, counted and added at a concentration of 5310 5 into 25 cm 2 culture