Polyploidy: occurrence in nature, mechanisms, and significance for the megakaryocyte-platelet system.

OBJECTIVE: Polyploidy, the state of having greater than the diploid content of DNA, has been recognized in a variety cells. Among these cell types, the megakaryocytes are classified as obligate polyploid cells, developing a polyploid DNA content regularly during the normal life cycle of the organism, while other cells may become polyploid only in response to certain stimuli. The objective of this review is to briefly describe the different cell cycle alterations that may lead to high ploidy, while focusing on the megakaryocyte and the importance of high ploidy to platelet level and function.

MATERIALS AND METHODS: Relevant articles appearing in scientific journals and books published in the United States and in Europe during the years 1910-1999 were used as resources for this review. We selected fundamental studies related to cell cycle regulation as well as studies relevant to the regulation of the endomitotic cell cycle in megakaryocytes. Also surveyed were publications describing the relevance of high ploidy to high platelet count and to platelet reactivity, in normal situations and in a disease state.

RESULTS: Different cells may achieve polyploidy through different alterations in the cell cycle machinery.

CONCLUSIONS: While upregulation of cyclin D3 further augments ploidy in polyploidizing megakaryocytes in vivo, future investigation should aim to explore how normal megakaryocytes may initiate the processes of skipping late anaphase and cytokinesis associated with high ploidy. In humans, under normal conditions, megakaryocyte ploidy correlates with platelet volume, and large platelets are highly reactive. This may not apply, however, to the disease state.