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, th e megakaryocytes are classified as obligate polyploid cells, developing a p olyploid DNA content regularly during the normal life cycle of the organism , while other cells may become polyploid only in response to certain stimul i. The objective of this review is to briefly describe the different cell c ycle alterations that may Lead to high ploidy, while focusing on the megaka ryocyte and the importance of high ploidy to platelet Level and function. Materials and Methods. Relevant articles appearing in scientific journals a nd books published in the United States and in Europe during the years 1910 -1999 were used as resources for this review. We selected fundamental studi es related to cell cycle regulation as well as studies relevant to the regu lation 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 alteratio ns in the cell cycle machinery. Conclusions. While upregulation of cyclin D3 further augments ploidy in pol yploidizing megakaryocytes in vivo, future investigation should aim to expl ore how normal megakaryocytes may initiate the processes of skipping late a naphase and cytokinesis associated with high ploidy, In humans, under norma l conditions, megakaryocyte ploidy correlates with platelet volume, and lar ge platelets are highly reactive. This may not apply, however, to the disea se state. (C) 2000 International Society for Experimental Hematology. Publi shed by Elsevier Science Inc.