Transforming growth factor inhibits erythropoiesis by blocking proliferation and accelerating differentiation of erythroid progenitors

Zermati, Yaël; Fichelson, Serge; Valensi, Françoise; Freyssinier, J M; Rouyer-Fessard, P; Cramer, EM; Guichard, J; Varet, Bruno; Hermine, Olivier

doi:10.1016/s0301-472x(00)00488-4

Cited by 150 publications

(122 citation statements)

References 40 publications

(34 reference statements)

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“…Normal regulation of proliferation, differentiation, and apoptosis is lost in cancer cells (Andreeff et al, 2000). Because these three aspects are interconnected (i.e., arrest of the cell-cycle is a prerequisite for differentiation, and differentiation ultimately results in cell death in many systems (Sorrentino et al, 1990;Umek et al, 1991;Morioka et al, 1998;Gandarillas et al, 1999;Zermati et al, 2000), DT exploits these associations and restores pathways that have been apparently lost during carcinogenesis. The typical clinical paradigm of DT, epitomized by all-trans-retinoic acid (ATRA) treatment of APML, requires months of pharmacological therapy.…”

Section: Discussionmentioning

confidence: 99%

Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells

et al. 2002

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Photodynamic therapy using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) may be applied to the treatment of neoplasms in a variety of organs. In order to enhance existing regimens of photodynamic therapy, we investigated the effects of adding differentiation therapy to photodynamic therapy in human prostate cancer cells in vitro. The objective of differentiation therapy per se is to reverse the lack of differentiation in cancer cells using pharmacological agents. The motivation for this study was to exploit the differentiation-dependent expression of some heme enzymes to enhance tumour cell toxicity of ALA-photodynamic therapy. A short course of differentiation therapy was applied to increase PpIX formation during subsequent ALA exposure. Using the synthetic androgen R1881, isomers of retinoic acid, and analogues of vitamin D for 3 to 4 days, exogenous ALA-dependent PpIX formation in LNCaP cells was increased, along with markers for growth arrest and for differentiation. As a consequence of higher PpIX levels, cytotoxic effects of visible light exposure were also enhanced. Short-term differentiation therapy increased not only the overall PpIX production but also reduced that fraction of cells that contained low PpIX levels as demonstrated by flow cytometry and fluorescence microscopy. This study suggests that it will be feasible to develop protocols combining short-term differentiation therapy with photodynamic therapy for enhanced photosensitisation.

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Section: Discussionmentioning

confidence: 99%

Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells

et al. 2002

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“…Transforming growth factor β1 (TGF-β1) is known to accelerate the erythroid differentiation, allowing full terminal differentiation toward enucleated red cells. 37,38 TGF-β1 also induces a massive inhibition of cell proliferation that mainly involves cell cycle arrest rather than apoptosis. 38 We observed similar effects, albeit to a lesser extent, in GD during in vitro erythropoiesis.…”

Section: Dyserythropoiesis In Gaucher Diseasementioning

confidence: 99%

“…37,38 TGF-β1 also induces a massive inhibition of cell proliferation that mainly involves cell cycle arrest rather than apoptosis. 38 We observed similar effects, albeit to a lesser extent, in GD during in vitro erythropoiesis. Because TGF-β1, or cytokines belonging to the same family (such as GDF-11 and GDF-15), represent autocrine factors released by erythroblasts, they could induce or impair the signaling pathways responsible for the dyserythropoiesis in GD.…”

Section: Dyserythropoiesis In Gaucher Diseasementioning

confidence: 99%

Unexpected macrophage-independent dyserythropoiesis in Gaucher disease

et al. 2016

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International audienceGaucher disease is a rare inherited disease caused by a deficiency in glucocerebrosidase leading to lipid accumulation in cells of mononuclear-macrophage lineage known as Gaucher cells. Visceral enlargement, bone involvement, mild anemia and thrombocytopenia are the major manifestations of Gaucher disease. We have previously demonstrated that the red blood cells from patients exhibit abnormal properties, which indicates a new role in Gaucher disease pathophysiology. To investigate whether erythroid progenitors are affected, we examined the in vitro erythropoiesis from the peripheral CD34+ cells of patients and controls. CD34− cells were differentiated into macrophages and co-cultivated with erythroblasts. We showed an accelerated differentiation of erythroid progenitors without maturation arrest from patients compared to controls. This abnormal differentiation persisted in the patients when the same experiments were performed without macrophages, which strongly suggested that dyserythropoiesis in Gaucher disease is secondary to an inherent defect in the erythroid progenitors. The accelerated differentiation was associated with reduced cell proliferation. As a result, less mature erythroid cells were generated in vitro in the Gaucher disease cultures compared to the control. We then compared the biological characteristics of untreated patients according to their anemic status. Compared to the non-anemic group, the anemic patients exhibit higher plasma levels of growth differentiation factor-15, a marker of ineffective erythropoiesis, but they had no indicators of hemolysis and similar reticulocyte counts. Taken together, these results demonstrated an unsuspected dyserythropoiesis that was independent of the macrophages and could participate, at least in part, to the basis of anemia in Gaucher disease

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“…The effects of retinoids on erythroid progenitors has been studied in CD34 þ hematopoietic progenitor cells, which consist of a heterogeneous population of CFU-GEMM, BFU-E and CFU-E, and in CD36 þ cells, which consist of intermediate and late erythroid progenitors (late BFU-E and CFU-E) in purified erythrocyte systems (Van Schravendijk et al, 1992;Zermati et al, 2000). All-trans retinoic acid was shown to stimulate human BFU-E colony formation, suggesting that retinoids were involved in erythropoiesis (Douer & Koeffler, 1982).…”

Section: Retinoids and Erythropoiesismentioning

confidence: 99%

The anemia of vitamin A deficiency: epidemiology and pathogenesis

Bloem²

2002

Eur J Clin Nutr

300

223

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Objective: To gain insight into vitamin A deficiency as a cause of anemia. Methods: Comprehensive review of the scientific literature. Results: Although vitamin A deficiency is recognized to cause anemia, 'vitamin A deficiency anemia' lacks complete characterization as a distinct clinical entity. Vitamin A appears to be involved in the pathogenesis of anemia through diverse biological mechanisms, such as the enhancement of growth and differentiation of erythrocyte progenitor cells, potentiation of immunity to infection and reduction of the anemia of infection, and mobilization of iron stores from tissues. Epidemiological surveys show that the prevalence of anemia is high in populations affected by vitamin A deficiency in developing countries. Improvement of vitamin A status has generally been shown to reduce anemia, but the actual public health impact on anemia is unclear. Conclusions: Further work is needed to elucidate the biological mechanisms by which vitamin A causes anemia. The inclusion of anemia as an outcome measure in future micronutrient intervention studies should help provide further insight into the anemia of vitamin A deficiency.

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Transforming growth factor inhibits erythropoiesis by blocking proliferation and accelerating differentiation of erythroid progenitors

Cited by 150 publications

References 40 publications

Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells

Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells

Unexpected macrophage-independent dyserythropoiesis in Gaucher disease

The anemia of vitamin A deficiency: epidemiology and pathogenesis

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