Cyclins and cell division kinases in megakaryocytic endomitosis.

Little is known concerning the mechanism by which megakaryocytes achieve their high levels of DNA content. Mature megakaryocytes show multiple 2-fold increases in DNA content, but the various levels of polyploidization exist within each of the morphologically recognizable classes. A number of studies have documented that the stimulatory actions of partially purified thrombopoietin or other cytokines on megakaryocyte DNA content both in vivo and in vitro. It is thus hypothesized that polyploidization is a crucial first step in megakaryocyte differentiation that is necessary for eventual cytoplasmic maturation and platelet production. Biochemically, there are 2 cell cycle regulatory points (either permissive or restrictive) which lead to polyploid DNA content in megakaryocytes; one regulatory point controls the increased DNA synthesis (presumably at the G1/S cell cycle boundary) and the other controls mitotic events, resulting in a single nucleus and an acytokinetic cell (the control point for this latter switch would be in early M-phase). Alterations in the biochemical control of these check points in other systems suggests that alterations in mitosis are among the first steps in endomitosis.