Functional and Morphological Differentiation Induction of a Human Megakaryoblastic Leukemia Cell Line ( MEG - Ols ) by Phorbol Diesters

The effect of differentiation induction by a tumor-promoting phorbol diester. 1 2-O-tetradecanoylphorbol-1 3-acetate (TPA) on a clonal human megakaryoblastic cell line. MEG01 s. was investigated. and a prominent response was demonstrated. The cells became weakly adherent, developed conspicuous cytoplasmic blebs. and displayed mature megakaryocytic characteristics by light microscopy such as the development of azurophilic cytoplasmic granules and a mosaic pattern of oxyphilic patches. multiplication of nuclei, and enhancement of the PAS reaction and alphanaphthyl acetate esterase staining. Ultrastructural studies demonstrated the development of prominent cytoplasmic blebs. budding of blebs. and multiplication of nuclei. Numerous granules with central nucleoids that are similar to a granules had developed as well as granules with high electron density and clearly demarcated zones. Surface marker analysis revealed a moderate increase in lgG Fe receptor levels and a profound decrease in C3 receptor sites. By an immunofluorescent technique using monoclonal and polyclonal antibodies. a dramatic change in the expression of several megakaryocyte-platelet-specific proteins was demonstrated. All the proteins that had been