K-252A-INDUCED POLYPLOIDIZATION AND DIFFERENTIATION OF A HUMAN MEGAKARYOCYTIC CELL-LINE, MEG-J - TRANSIENT ELEVATION AND SUBSEQUENT SUPPRESSION OF CYCLIN B-1 AND CDC2 EXPRESSION IN THE PROCESS OF POLYPLOIDIZATION

Megakaryocytes are unique haemopoietic cells which undergo DNA replica tion, giving rise to polyploid cells. However, little is known about t he mechanism of megakaryocytic polyploidization. To address this issue , we used the human megakaryocytic cell line Meg-J. In the presence of K-252a (an indolocarbasole derivative), Meg-J cells stopped prolifera tion and exhibited additional megakaryocytic features, including morph ological changes, polyploidization, and increases in the levels of sur face expression of platelet glycoprotein (GP) IIIb/IIIa and GPIb. Thro mbopoietin (TPO) promoted the K-252a-induced polyploidization and mega karyocytic differentiation. In the process of K-252a-induced polyploid ization, levels of expression of both cdc2 and cyclin B-1 were elevate d transiently and subsequently decreased. This suggested that the poly ploidization process in Meg-J cells was at least in part associated wi th a transient elevation and subsequent decrease in the expression of cdc2/cyclin B-1 complex, a critical kinase involved in G2/M cell cycle transition.