PHORBOL ESTER-INDUCED DIFFERENTIATION OF HUMAN LYMPHOBLASTIC-T CELL-LINE HPB-ALL

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (9) , 3843-3850
Abstract
12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter, induced phenotypic differentiation in the human acute lymphocytic leukemia T-cell line, HPB-ALL. Within 30 min of seeding in the presence of TPA, the cells formed a smooth round shape. After a 7-day exposure to TPA, most of the cells became smaller and reminiscent of large or atypical lymphocytes. EM analysis evidenced morphological differentiation in TPA-treated HPB-ALL cells. T antigens stained with monoclonal antibody OKT6 were dramatically reduced while Leu2a-positive cells were increased in the TPA-treated HPB-ALL cells. However, OKT3-positive cells did not appear in these TPA-treated cells for up to 7 days. Upon TPA-induced phenotypic differentiation, the growth rate of cells was significantly inhibited, their ability to incorporate DNA and RNA via 3H-labeled precursors was reduced, their ability to bind sheep red blood cell rosettes was significantly increased, and the proportion of terminal deoxynucleotidyl transferase-positive cells was decreased. [Differentiation induction in these cells may be of therapeutic value and may also provide insights into the mechanism of differentiation and the origin and pathogenesis of leukemias.].