Phorbol ester-induced differentiation of a non-T, non-B leukemic cell line: model for human lymphoid progenitor cell development.

The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was tested for its ability to induce phenotypic changes in the human non-T,. non-B ALL cell line REH. Cells were cultured with nanogram concentrations of TPA for up to 48 hr, and were analyzed by indirect immunofluorescence with a panel of monoclonal antibodies and an antibody to the enzyme terminal deoxynucleotidyl transferase (TdT). TPA induced REH cells to express the leukemia-associated antigen, p24 (detected with monoclonal antibody BA-2; p24/BA-2) by 8 hr of culture, with induction complete by 24 hr. TPA-treated cells also underwent a concomitant decrease in the expression of TdT when analyzed enzymatically or by immunofluorescence. Analysis of TPA-treated cells with monoclonal antibodies BA-1 (detecting a B cell-associated antigen), 7.2 (detecting a monomorphic HLA-DR antigen), or OKT11 (detecting a structure closely associated with the E receptor) showed no change compared to controls. In addition there was no detectable cytoplasmic immunoglobulin in control or TPA-treated cells. These results show clearly that TPA is capable of inducing phenotypic changes in REH cells. Such changes may reflect the differentiation-linked expression of antigens present in normal bone marrow lymphoid progenitor cells.