Differentiation of human myeloid leukemia cell lines induced by tumor-promoting phorbol ester (TPA). I. Changes of the morphology, cytochemistry and the surface differentiation antigens analyzed with monoclonal antibodies.

Human myeloid leukemia cell lines ML-1, ML-2, ML-3, promyelocytic leukemia cell line HL-60 and histiocytic lymphoma cell line U-937 were induced to differentiate by 0.5-10 ng/ml (0.8-16 nM) 12-O-tetradecanoylphorbol-13-acetate (TPA). After 48-72 h of induction, changes of the morphology, cytochemistry and of the antigenic phenotype of induced and control cells were studied using a panel of monoclonal antibodies against granulocytic, monocytic, HLA-ABC and HLA-DR antigens in indirect immunofluorescence. Cells of the TPA-treated cultures acquired morphological, cytochemical and antigenic markers of monocytes/macrophages, as surface adherence, alpha-naphthyl acetate esterase (alpha-NE) and acid phosphatase activity and the expression of monocytic antigens detected with monoclonal antibodies 63D3, FMC 17, B 44.1, B 52.1 and anti-Mol. During differentiation in vitro induced by TPA, also loss of HLA-DR antigens and diminution of antigen of cell activation were detected with antibodies L 243 and 4F2. The expression of granulocytic antigens was only slightly diminished and the expression of HLA-ABC antigens was not changed by TPA-treatment. There were differences in the percentage of cells induced to differentiate among the lines of different origin and even among the lines ML-1, ML-2 and ML-3, established from a single patient with acute myeloid leukemia. After treatment of cultures with 5 ng/ml TPA for 72 h DNA synthesis was inhibited to 60-80%.