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Transcription Factors in Erythroid Differentiation

FLI-1 is a suppressor of erythroid differentiation in human hematopoietic cells

Leukemia volume 14, pages 439–445 (2000)Cite this article

Abstract

The FLI-1 oncogene, a member of the ETS family of transcription factors, is associated with both normal and abnormal hematopoietic cell growth and lineage-specific differentiation. We have previously shown that overexpression of FLI-1 in pluripotent human hematopoietic cells leads to the induction of a megakaryocytic phenotype. In this report we show that FLI-1 also acts as an inhibitor of erythroid differentiation. Following the induction of erythroid differentiation, pluripotent cells express reduced levels of FLI-1. In contrast, when FLI-1 is overexpressed in these cells, the levels of erythroid markers are reduced. The ability of FLI-1 overexpressing cells to respond to erythroid-specific inducers such as hemin and Ara-C is also inhibited, and the uninduced cells show a reduced level of the erythroid-associated GATA-1 transcription factor mRNA. Furthermore, expression of a GATA-1 promoter-driven reporter construct in K562 cells is inhibited by co-transfection with a construct expressing FLI-1. Our results support the hypothesis that FLI-1 can act both positively and negatively in the regulation of hematopoietic cell differentiation, and that inhibition of GATA-1 expression may contribute to FLI-1-mediated inhibition of erythroid differentiation.

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Acknowledgements

We wish to thank Karen Cannon for preparation of the manuscript, Louise Finch, Flow Cytometry Laboratory, Clinical Services Program, SAIC, for performing flow cytometry analysis, and Sandra Ruscetti for providing GATA-1 promoter constructs and for helpful discussions. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. N01-CO-56000. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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Authors and Affiliations

  1. Intramural Research Support Program, SAIC Frederick, Frederick, MD, USA

    M Athanasiou

  2. IMBB-FORTH and Medical School, University of Crete, Heraklion, Crete, Greece

    G Mavrothalassitis

  3. Division of Basic Sciences, Basic Research Laboratory, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD, USA

    L Sun-Hoffman & DG Blair

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Athanasiou, M., Mavrothalassitis, G., Sun-Hoffman, L. et al. FLI-1 is a suppressor of erythroid differentiation in human hematopoietic cells. Leukemia 14, 439–445 (2000). https://doi.org/10.1038/sj.leu.2401689

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