Distinctive phorbol ester-induced morphological and surface antigen changes in mycosis fungoides, the Sézary syndrome, and adult T-cell leukemia.
Clinical and pathological studies of cutaneous T-cell lymphomas (CTCL) reveal variations in tumor cell morphology and surface membrane phenotype that are of diagnostic and prognostic importance. Our study investigates blastic transformation and surface antigen change on CTCL cells in vitro under the influence of tumor-promoting phorbol ester (TPA) and phytohemagglutinin. Both agents transformed tumor cells with cerebriform nuclei into blast cells within 5 days; however, Sézary cells were somewhat resistant to transformation with phytohemagglutinin. Multinucleated cells with prominent nucleoli resembled Reed-Sternberg cells of Hodgkin's disease. These morphological changes simulated the appearance of the aggressive tumor stage of mycosis fungoides. During blastic transformation, the erythrocyte rosette receptor was induced by TPA on sheep erythrocyte-rosette-negative Sézary cells from one patient. During the first 24 hr in vitro, Sézary and MF cells stimulated by TPA lost Leu 3a (T4) antigen while maintaining original high levels of Leu 1 antigen. In contrast, leukemia cells from patients with adult T-cell leukemia (ATL) were resistant to modulation of Leu 3a antigen by TPA; 3A1 antigen on CTCL and ATL cells was unaffected by TPA. Blastic transformation of CTCL cells was observed with both TPA and phytohemagglutinin, but helper T-cell antigen Leu 3a (T4) and erythrocyte rosette receptor changes occurred only with TPA. Thus, blastic transformation and surface differentiation were not directly related. These results provide a possible model for the study of blastic transformation and surface antigen/receptor variation in CTCL. They also may provide an independent test for the distinction of CTCL and ATL in vitro. Finally, they illustrate the relative resistance of ATL to surface antigen modulation as previously shown for Tac antigen modulation by anti-Tac antibody.
D000328:Adult; D000954:Antigens, Surface / Q000032:analysis*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D006801:Humans; D007700:Kinetics; D007938:Leukemia / Q000276:immunology / Q000503:physiopathology*; D009182:Mycosis Fungoides / Q000276:immunology / Q000503:physiopathology*; D010641:Phenotype; D010704:Phorbols / Q000633:toxicity*; D012751:Sezary Syndrome / Q000276:immunology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D000954:Antigens, Surface; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate