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Autocrine transforming growth factor-β regulation of hematopoiesis: many outcomes that depend on the context

Oncogene volume 24, pages 5751–5763 (2005)Cite this article

Abstract

Transforming growth factor-β (TGF-β) is a pleiotropic regulator of all stages of hematopoieis. The three mammalian isoforms (TGF-β1, 2 and 3) have distinct but overlapping effects on hematopoiesis. Depending on the differentiation stage of the target cell, the local environment and the concentration and isoform of TGF-β, in vivo or in vitro, TGF-β can be pro- or antiproliferative, pro- or antiapoptotic, pro- or antidifferentiative and can inhibit or increase terminally differentiated cell function. TGF-β is a major regulator of stem cell quiescence, at least in vitro. TGF-β can act directly or indirectly through effects on the bone marrow microenvironment. In addition, paracrine and autocrine actions of TGF-β have overlapping but distinct regulatory effects on hematopoietic stem/progenitor cells. Since TGF-β can act in numerous steps in the hematopoietic cascade, loss of function mutations in hematopoeitic stem cells (HSC) have different effects on hematopoiesis than transient blockade of autocrine TGF-β1. Transient neutralization of autocrine TGF-β in HSC has therapeutic potential. In myeloid and erythroid leukemic cells, autocrine TGF-β1 and/or its Smad signals controls the ability of these cells to respond to various differentiation inducers, suggesting that this pathway plays a role in determining the cell fate of leukemic cells.

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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. NO1-CO-56000.

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  1. Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, 21702-1201, MD, USA

    Francis W Ruscetti

  2. Department of Medical Laboratory Sciences, Hashemite University, Zarqa, Jordan

    Salem Akel

  3. Hemogenix, Inc., Colorado Springs, CO, USA

    Stephen H Bartelmez

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Ruscetti, F., Akel, S. & Bartelmez, S. Autocrine transforming growth factor-β regulation of hematopoiesis: many outcomes that depend on the context. Oncogene 24, 5751–5763 (2005). https://doi.org/10.1038/sj.onc.1208921

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