Phorbol ester-induced differentiation of chronic lymphocytic leukaemia cells

Tötterman, T.H.; Nilsson, K.; Sundström, C.

Nature 288(5787): 176-178


ISSN/ISBN: 0028-0836
PMID: 7432517
Accession: 006103537

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The croton oil-derived tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) exerts pleiotropic effects on the differentiation and proliferation of normal and malignant animal and human cells in vitro. The effect of TPA on chronic lymphocytic leukemia (CLL) biopsy cells in vitro is reported. In 4 of 5 CLL patients studied, TPA induced the appearance of 90-100% lymphoblastoid and plasmacytoid cells after 4 days of culture. Under the influence of TPA, 86-97% of the cells expressed with time increasing amounts of intracytoplasmic Ig (C-Ig) of the same phenotype as that detected on the surface (S-Ig) of fresh, non-induced CLL cells. A parallel decrease in monoclonal S-Ig density and DNA synthesis of the CLL cells was observed. EM studies showed a maturation towards plasma cells. TPA is capable of inducing differentiation of CLL cells in vitro.