The Effects of TGFβ on Haemopoietic Cells

Hampson, J.P.; Ponting, I. L. O.; Cook, Natalie; Vodinelich, L.; Redmond, S.; Roberts, Anita B.; Dexter, T. M.

doi:10.3109/08977198909029128

Cited by 33 publications

(11 citation statements)

References 53 publications

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“…As already shown by Hampson and coworkers [7], the modulatory effect of TGF-/~ resulting in suppressed or stimulated hematopoiesis is apparently not due to the number of receptors expressed in defined states of progenitor cells, but may vary according to their state of differentiation.…”

Section: Discussionmentioning

confidence: 74%

Modulation of hematopoietic colony formation of stem cells in peripheral blood by anti-TGF-β in patients with severe immunosuppression

et al. 1991

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The influence of transforming growth factor-beta (TGF-beta) on hematopoiesis has been evaluated by adding blocking antibodies against TGF-beta to colony forming assays (CFU-c). When optimum concentrations of recombinant growth factors, granulocyte-macrophage colony stimulating factor (GM-CSF), and interleukin-3 (IL-3) were added to stem cells from the peripheral blood of healthy individuals and certain patients with tumors or HIV infection, the anti-TGF-beta capable of blocking 5 ng/ml of active TGF-beta had no significant influence on erythroid or myeloid colony formation. However, in certain immunosuppressed individuals, anti-TGF-beta resulted in a significant decrease of erythroid colony formation and slight suppression of myeloid colony formation. The significant inhibition of hematopoiesis by plasma of HIV patients could be due to the presence of active forms of TGF-beta. The results of the blocking experiments are consistent with the concept that TGF-beta in low concentrations is essential for erythropoiesis and myelopoiesis but that higher levels of TGF-beta primarily inhibit erythropoiesis in vitro. TGF-beta serves as a coordinating factor when efficient recruitment of granulocytes and monocytes is more essential than erythropoiesis and stem cell growth.

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Section: Discussionmentioning

confidence: 74%

Modulation of hematopoietic colony formation of stem cells in peripheral blood by anti-TGF-β in patients with severe immunosuppression

et al. 1991

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“…We have found that it inhibits the response of multipotent cells to IL-3. It also inhibits GM-CFC colony formation stimulated by IL-3 or M-CSF, but not those stimulated by GM-CSF [49]. Its activity, therefore, appears to be both differentiation-specific and growth factor related.…”

Section: Negative Regulation Of Haemopoiesismentioning

confidence: 89%

The role of growth factors in haemopoietic development: Clinical and biological implications

Daniel

Dexter

1989

Cancer Metast Rev

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Mature blood cells of all lineages are derived from a single class of cell, the haemopoietic stem cell. Stem cells are pluripotent and capable of almost limitless self-renewal. In the bone marrow they form part of a hierarchy that includes progenitor cells, which are more restricted in the lineages their progeny can adopt, and precursor cells, which are committed to differentiation. The mechanisms that regulate progression through this hierarchy are not fully understood, but evidence suggests that both bone marrow stromal cells and soluble growth factors have a role in controlling haemopoiesis. Four growth factors act on progenitor cells to promote their survival, proliferation, differentiation, and maturation: interleukin-3 (IL-3), granulocyte/macrophage-colony stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and macrophage-CSF (M-CSF). They can also activate the function of mature cells. Considerable overlap is found in the target cells for these four growth factors. We have found that growth factors acting in synergy can recruit more primitive cells than had previously been appreciated. These factors can also determine the lineage that the progeny of multipotential progenitors will adopt. Thus, colony-stimulating factors (CSFs) have the potential to regulate the development of primitive haemopoietic cells in vivo. The properties of CSFs have made them useful in treating malignant disease: G-CSF, in particular, has been used to reduce the period of neutropaenia that follows cytotoxic therapy for various malignancies. The success of these early trials gives ground for cautious optimism about the clinical use of these compounds.

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“…Some absolutely require the presence of growth factors for their growth and survival while others are growth factor independent. Regardless of the factor used to stimulate cell growth of murine leukemic cell lines, their growth is inhibited by TGF-b , while differentiation-blocked (TGF-bR positive) cell lines were insensitive to TGF-b effects (Hampson et al, 1989). It has been proposed that cells with a more transformed phenotype (differentiation blocked) become refractory to the effects of TGF-b and possibly escape negative regulation.…”

Section: Tgf-b Signaling Pathway In Leukemia: Rare Mutational Inactivmentioning

confidence: 99%

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

2005

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The Effects of TGFβ on Haemopoietic Cells

Cited by 33 publications

References 53 publications

Modulation of hematopoietic colony formation of stem cells in peripheral blood by anti-TGF-β in patients with severe immunosuppression

Modulation of hematopoietic colony formation of stem cells in peripheral blood by anti-TGF-β in patients with severe immunosuppression

The role of growth factors in haemopoietic development: Clinical and biological implications

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

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