Functional roles of several Ets transcription factors in megakaryocytic and erythroid differentiation of the human chronic myelogenous leukemia cell line K562 was investigated. When K562 cells were induced to differentiate into the megakaryocyte lineage by treatment with TPA, the expression of the c-ets-1, Fli-1 and TEL2 genes was increased, and that of the TEL gene was decreased at the onset of differentiation. When the cells were induced to differentiate into the erythroid lineage by treatment with Hemin, expression of the c-ets-1 gene was increased, and that of the Fli-1 and TEL genes was decreased. To investigate the role of TEL in the growth and differentiation of K562 cells, we introduced an expression plasmid containing the TEL gene into the cells. Overexpression of TEL in K562 cells leads to inhibition of the endogenous expression of megakaryocyte-specific GPIIb and GPIbα genes, and inhibition of cell growth. DNA array analysis revealed that expression of genes such as the RhoG and D4-GDI genes was down-regulated in TEL-overexpressing cells, while that of the representative growth-related genes such as the c-myc, c-fos and c-jun genes was not remarkably changed. These results suggest that several Ets family transcription factors are implicated in megakaryocytic and erythroid differentiation of K562 cells and TEL inhibits the expression of some megakaryocyte-specific genes and growth in K562 cells.