Significance of polyploidy in megakaryocytes and other cells in health and tumor disease

Abstract

Polyploidy--the doubling of chromosome sets of cells caused by a stop of mitosis at different levels of the mitotic cycle--is a phenomenon widely observed in plants, protozoa, metazoa, and animals. In man obligate polyploid tissues are found in liver parenchyma, heart muscle cells, and bone marrow megakaryocytes. Polyploidy occurs mostly in stable and highly differentiated cells and tissues. Besides age, stimulation of proliferation and increased metabolic function lead to polyploidization in these organs. Aneuploidy, however, is exclusively found in tumor cells. Megakaryocyte differentiation and polyploidy are controlled by thrombopoietin-like activities, of which the loci of production are still unknown. Megakaryocytes are unique among polyploid mammal cells. On the precursor level they maintain their proliferative activity independently of the mammal's age. Once having entered the incomplete mitotic cycle they stop cytokinesis and develop into highly polyploid cells. Polyploidization of megakaryocytes is the basic requirement for establishing highly effective hemostasis in mammals, which exhibit blood circulation based on high blood pressures. Every polyploidization results in increased production of membrane materials with which the platelet becomes endowed. By shedding cytoplasmic fragments approximately 3000 platelets are set free from a 32c megakaryocyte, compared with only 16 nucleated thrombocytes by mitotic division. There is further evidence that the heterogeneity of platelets mostly depends on the different polyploidy classes of the megakaryocytes from which they are derived. Changes in the polyploidy pattern of megakaryocytes could therefore have consequences for hemostatic disorders in several human diseases, particularly in malignancy.