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During the development of the megakaryocyte lineage, the megakaryoblasts give rise to megakaryocytes which undergo repeated S phases in the absence of cytokinesis (endomitosis). The cellular oncogene  myc  plays a central role in the proliferation and differentiation of several cell types. In a previous study, we generated transgenic mice carrying c‐ myc  fused to the estrogen receptor under the control of the platelet factor four (PF4) megakaryocyte‐specific promoter. The bone marrow of female transgenic mice, but not of male mice, displayed increased megakaryopoiesis. Here we report that β‐estradiolinduced activation of c‐ myc  in cultured bone marrow cells derived from male or female transgenic mice resulted in prolonged survival of the cells in vitro. Addition of a cocktail of hemopoietic growth factors to β‐estradiol‐treated cells, including interleukin 6 (IL‐6), IL‐3 and stem cell factor further improved the survival time in culture and increased the percentage of large mature cells, but did not result in immortalization. The majority of these PF4‐expressing cells, however, did not reach the differentiation stage at which acetylcholinesterase is expressed and did not appear as large megakaryocytes. We conclude that cultured megakaryocytes overexpressing  myc  are induced to proliferate, but have a limited potential to fully differentiate. Under these conditions, cyclin D3 was downregulated while the level of cyclin A was slightly upregulated.

A New Transgenic Mouse Model for the Study of Cell Cycle Control in Megakaryocytes