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Myb is required for self-renewal in a model system of early hematopoiesis

Oncogene volume 19, pages 1196–1205 (2000)Cite this article

Abstract

In hematopoiesis, self-renewal, proliferation, differentiation and apoptosis represent opposing decisions made by stem cells and progenitor cells, which when dysregulated can result in leukaemia. Here, we have investigated the function of Myb proteins in regulating these key cellular decisions, using the cell line FDCP-mix A4 as a model of early hematopoiesis. High concentrations of IL-3 in these cells favour self-renewal over differentiation and apoptosis. However when endogenous Myb activity was inhibited with an inducible dominant interfering protein, self-renewal was replaced by apoptosis and differentiation. Differentiation was to granulocytes and monocyte/macrophages and was closely associated with a G1-S phase block in the cell cycle. As for normal hematopoiesis, cytokine-induced terminal differentiation of FDCP-mix cells is associated with concomitant proliferation prior to its completion. However, when Myb activity was inhibited during this process, proliferation and survival were both reduced, resulting in a much lower yield of mature cells. These results indicate multiple cellular roles of Myb proteins during normal hematopoiesis.

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Acknowledgements

We thank Peter Rathjen (University of Adelaide) for providing a GBX2 probe, Lyn Healy for technical advice and help for the culture of FDCP-mix cells, and Claire Heyworth and Dorothy Gagen (Paterson Institute, Manchester) for provision of cells and advice on FDCP-mix differentiation. This work was supported by a postdoctoral fellowship from the Leukemia Research Fund to JR White and the Cancer Research Campaign (K Weston).

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  1. CRC Centre for Cell and Molecular Biology, Institute of Cancer Research, London, SW3 6JB, UK

    Jonathan R White & Kathleen Weston

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White, J., Weston, K. Myb is required for self-renewal in a model system of early hematopoiesis. Oncogene 19, 1196–1205 (2000). https://doi.org/10.1038/sj.onc.1203394

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