Induction of plasmacytoid differentiation by phorbol ester in B-cell lymphoma cell lines bearing 8;14 translocations.

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RESUMO

At nanomolar concentrations, phorbol 12-myristate 13-acetate induced differentiation in a human Epstein-Barr virus-negative B-cell line, JD 38, derived from an undifferentiated lymphoma and containing an 8;14 translocation. The changes induced by phorbol 12-myristate 13-acetate were consistent with differentiation towards plasma cells and included (i) a marked increase (30-fold) in IgM secretion; (ii) a decrease in the nuclear/cytoplasmic ratio associated with the development of a single prominent nucleolus instead of multiple nucleoli; (iii) the development of parallel arrays of rough endoplasmic reticulum, eccentric nuclei, and marginated heterochromatin; (iv) a reduction in the expression of surface markers, including common acute lymphoblastic leukemia antigen, IgM, and C3 receptors. Essentially all cells showed plasmacytoid differentiation, although the degree varied. Rare cells (less than 1%) appeared to be terminally differentiated into plasma cells. The increase in secreted IgM was preceded by a small increase in mu-chain RNA, with an increase in the ratio of secreted to membrane form. A small increase in c-myc RNA was also detected with differentiation. This might reflect coordinate regulation of the transcription of immunoglobulin and the translocated c-myc gene. Thus, the maturational arrest of this lymphoma cell line can be overcome with phorbol 12-myristate 13-acetate, indicating that translocation of the c-myc gene does not permanently block the capacity for differentiation. Further, this gene continues to be expressed to at least the same level during cell maturation. Similar ultrastructural changes were induced by phorbol 12-myristate 13-acetate in four of seven additional lines studied.

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