ArticleAmerican journal of hematology2014
FOXO3-mTOR metabolic cooperation in the regulation of erythroid cell maturation and homeostasis.
Article in American journal of hematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Dual inhibition of glycolysis and glutaminolysis by targeting FOXO3 for hepatocellular carcinoma treatment.Oncogene · 2026Article
- Mutant SRSF2-associated impaired erythropoiesis is defined by increased mTORC1 signaling due to FYN missplicing.Leukemia · 2026Article
- Targeting erythroid progenitor cell metabolism to enhance cancer immunotherapy.NPJ precision oncology · 2026Review
- ILF3 regulates erythroid differentiation: A single-cell transcriptomic analysis and cellular experiment.PloS one · 2026Article
- Metabolic Control of Stem Cell Function: Insights into Amino Acid-Driven Mechanisms.Stem cell reviews and reports · 2025Review
- Anemia and malnutrition in geriatric hospitalized patients: a cross-sectional retrospective study.BMC geriatrics · 2025Article
- Sirolimus modulates the erythroid differentiation of K562 cells by upregulating SHP1.Annals of hematology · 2025Article
- Generation of mature epicardium derived from human-induced pluripotent stem cells via inhibition of mTOR signaling.Nature communications · 2025Article
- Mitapivat metabolically reprograms human β-thalassemic erythroblasts, increasing their responsiveness to oxidation.Blood advances · 2025Article
- Mitoxantrone ameliorates ineffective erythropoiesis in a β-thalassemia intermedia mouse model.Blood advances · 2024Article
- Yohimbine Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation and Migration via FOXO3a Factor.International journal of molecular sciences · 2024Article
- A Review of Key Regulators of Steady-State and Ineffective Erythropoiesis.Journal of clinical medicine · 2024Review
- Metabolic regulation of erythrocyte development and disorders.Experimental hematology · 2024Article
- Immunoregulation role of the erythroid cells.Frontiers in immunology · 2024Review
- AZD8055 Is More Effective Than Rapamycin in Inhibiting Proliferation and Promoting Mitochondrial Clearance in Erythroid Differentiation.Analytical cellular pathology (Amsterdam) · 2024Article
- Metformin as a Fetal Hemoglobin Inducer in Non-transfusion Dependent Thalassemia Patients.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2024Article
- Elevated CDKN1A (P21) mediates β-thalassemia erythroid apoptosis, but its loss does not improve β-thalassemic erythropoiesis.Blood advances · 2023Article
- FOXO family isoforms.Cell death & disease · 2023Review
- Loss of miR-144/451 alleviates β-thalassemia by stimulating ULK1-mediated autophagy of free α-globin.Blood · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Ineffective erythropoiesis is observed in many erythroid disorders including β-thalassemia and anemia of chronic disease in which increased production of erythroblasts that fail to mature exacerbate the underlying anemias. As loss of the transcription factor FOXO3 results in erythroblast abnormalities similar to the ones observed in ineffective erythropoiesis, we investigated the underlying mechanisms of the defective Foxo3(-/-) erythroblast cell cycle and maturation. Here we show that loss of Foxo3 results in overactivation of the JAK2/AKT/mTOR signaling pathway in primary bone marrow erythroblasts partly mediated by redox modulation. We further show that hyperactivation of mTOR signaling interferes with cell cycle progression in Foxo3 mutant erythroblasts. Importantly, inhibition of mTOR signaling, in vivo or in vitro enhances significantly Foxo3 mutant erythroid cell maturation. Similarly, in vivo inhibition of mTOR remarkably improves erythroid cell maturation and anemia in a model of β-thalassemia. Finally we show that FOXO3 and mTOR are likely part of a larger metabolic network in erythroblasts as together they control the expression of an array of metabolic genes some of which are implicated in erythroid disorders. These combined findings indicate that a metabolism-mediated regulatory network centered by FOXO3 and mTOR control the balanced production and maturation of erythroid cells. They also highlight physiological interactions between these proteins in regulating erythroblast energy. Our results indicate that alteration in the function of this network might be implicated in the pathogenesis of ineffective erythropoiesis.
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Registered trials
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