Freshly isolated human
leukemia cells have been shown in the past to display varying in vitro responses to
phorbol diesters, depending on their cell type. Specific receptors for the
phorbol diesters have been demonstrated on numerous different cells. This study was designed to characterize the receptors for
phorbol diesters on
leukemia cells freshly isolated from patients with different kinds of
leukemia and to determine if differences in binding characteristics for
tritium-labeled
phorbol 12,13-dibutyrate (3H-PDBu) accounted for the different cellular responses elicited in vitro by
phorbol diesters. Cells from 26 patients with different kinds of
leukemia were studied. PDBu or
phorbol 12-myristate 13-acetate (PMA) caused cells from patients with
acute myeloblastic leukemia (AML), acute promyelocytic (APML), acute myelomonocytic (AMML), acute monocytic (AMoL),
acute erythroleukemia (AEL),
chronic myelocytic leukemia (CML) in
blast crisis (myeloid), acute undifferentiated
leukemia (AUL), and
hairy cell leukemia (HCL) (n = 15) to adhere to
plastic and spread. However, they caused no adherence or spreading and only slight aggregation of cells from patients with
acute lymphocytic leukemia (ALL),
chronic lymphocytic leukemia (CLL), or CML-
blast crisis (lymphoid) (n = 11). All
leukemia cells studied, irrespective of cellular type, displayed specific receptors for 3H-PDBu. The time courses for binding by all
leukemia types were similar, with peak binding at 5-10 min at 37 degrees C and 120 min at 4 degrees C. The binding affinities were similar for patients with ALL (96 +/- 32 nM, n = 4), CLL (126 +/- 32 nM, n = 6), and acute nonlymphoid
leukemia (73 +/- 14 nM, n = 11). Likewise, the numbers of specific binding sites/cell were comparable for the patients with ALL (6.2 +/- 1.3 X 10(5) sites/cell, n = 4), CLL (5.0 +/- 2.0 X 10(5) sites/cell, n = 6), and acute nonlymphoid
leukemia (4.4 +/- 1.9 X 10(5) sites/cell, n = 11). Thus, the differing responses to
phorbol diesters of various types of freshly isolated
leukemia cells appear to be due to differences other than initial
ligand-receptor binding.