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Transforming growth factor-β signaling in normal and malignant hematopoiesis

Leukemia volume 17, pages 1731–1737 (2003)Cite this article

Abstract

Transforming growth factor-β (TGF-β) is perhaps the most potent endogenous negative regulator of hematopoiesis. The intracellular signaling events mediating the effects of TGF-β are multiple, involving extensive crosstalk between Smad-dependent and MAP-kinase-dependent pathways. We are only beginning to understand the importance of the balance between these cascades as a determinant of the response to TGF-β, and have yet to determine the roles that disruption in TGF-β signaling pathways might play in leukemogenesis. This review summarizes current knowledge regarding the function of TGF-β in normal and malignant hematopoiesis. The principal observations made by gene targeting studies in mice are reviewed, with an emphasis on how a disruption of this pathway in vivo can affect blood cell development and immune homeostasis. We overview genetic alterations that lead to impaired TGF-β signaling in hematopoietic neoplasms, including the suppression of Smad-dependent transcriptional responses by oncoproteins such as Tax and Evi-1, and fusion proteins such as AML1/ETO. We also consider mutations in genes encoding components of the core cell cycle machinery, such as p27Kip1 and p15INK4A, and emphasize their impact on the ability of TGF-β to induce G1 arrest. The implications of these observations are discussed, and opinions regarding important directions for future research on TGF-β in hematopoiesis are provided.

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  1. Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD, USA

    S-J Kim & J Letterio

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  1. S-J Kim
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Kim, SJ., Letterio, J. Transforming growth factor-β signaling in normal and malignant hematopoiesis. Leukemia 17, 1731–1737 (2003). https://doi.org/10.1038/sj.leu.2403069

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