Analysis of phorbol ester stimulated human megakaryocyte development

B. J. Roth, G. W. Sledge, J. E. Straneva, J. Brandt, M. Goheen, R. Hoffman

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Megakaryocytes are relatively rare components of human bone marrow, making the study of their maturation difficult. Phorbol esters can act as differentiating agents in a number of cell systems including murine megakaryocytes. We report the effects of phorbol esters on the previously described long-term human megakaryocytic leukemia cell culture, EST-IU. While two nontransforming phorbols fail to affect these cells, the transforming phorbol 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a phenotype with characteristics of more mature megakaryocytes in a dose-related manner. This phenotype includes an increased adherence to untreated plastic or glass, polyploidization, an increase in cell size, and increased expression of both platelet glycoproteins and factor VIII-related antigen. Two-color flow cytometric analysis allowed simultaneous determinations of DNA content and the expression of surface membrane antigens or alpha-granule constituents, providing evidence that nuclear, membrane, and cytoplastic maturation occur in parallel in this cellular system. TPA-induced maturation of EST-IU cells provides an important new cellular model for the further study of human megakaryocyte development.

Original languageEnglish
Pages (from-to)202-207
Number of pages6
Issue number1
StatePublished - 1988


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