INCREASED EXPRESSION OF THE ETS-RELATED TRANSCRIPTION FACTOR FLI-1 ERGB CORRELATES WITH AND CAN INDUCE THE MEGAKARYOCYTIC PHENOTYPE/

The human leukemia cell line K562 can be induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) to differentiate along the megakaryocytic pat hway, generating morphological changes and increased expression of lin eage-specific surface markers. We report that TPA-treated K562 cells a lso express higher levels of FLI-1/ERGB, a member of the ETS family of transcription factors. Furthermore, introduction of a retroviral cons truct expressing human FLI-1/ERGB into K562 cells induces changes simi lar to those seen following TPA treatment, including increased adheren ce to the surface of the culture vessel and altered size and morpholog y. Infected cells exhibit higher levels of the megakaryocyte marker CD 41a and, to a lesser extent, CD49b. These markers, as well as virally encoded FLI-1/ERGB-specific RNA and protein, are expressed at the high est levels in the attached cell population, while the growth rate of a dherent cells is reduced, and the fraction of cells in G(0)-G(1) is in creased. FLI-1/ERGB virus-infected cells also exhibit increased expres sion of hemoglobin, a marker of erythroid differentiation. Our results suggest FLI-1/ERGB plays a role in controlling differentiation and ge ne expression along the megakaryocyte/platelet pathway, and further im plicate ETS-related genes in the control of multiple developmentally r egulated hematopoietic genes.