ArticleScience translational medicine2018
Thrombopoietin receptor-independent stimulation of hematopoietic stem cells by eltrombopag.
Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 66 citations in OpenAlex.
- Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase II/III, multicentre, open-label study.British journal of haematology · 2021Trial
- Eltrombopag for patients with moderate aplastic anemia or uni-lineage cytopenias.Blood advances · 2020Trial
- From Iron to Depression: The Crosstalk Between the Periphery and Brain.Neuroscience bulletin · 2026Review
- Evolving Patterns of TPO-RA Use in Children: A Decade of Single-Centre Experience and Narrative Review.International journal of molecular sciences · 2026Review
- Loss of Hfe impairs hematopoietic stem and progenitor cell function.Blood. Red cells & iron · 2026Article
- Case Report: A rare case of primary graft failure after autologous stem cell transplant for mantle cell lymphoma rescued with darbepoetin, eltrombopag, and cyclosporine.Frontiers in transplantation · 2026Article
- Cell phenotypic conversion and fate change during the host defense response, tissue injury and repair.Pharmacology & therapeutics · 2026Review
- Iron and the immune system.Nature reviews. Immunology · 2025Review
- Effective treatment of refractory aplastic anemia with romiplostim after failure of multiple thrombopoietin receptor agonists: a single-center retrospective study.Annals of medicine · 2025Article
- Iron deficiency anemia following long-term eltrombopag treatment for aplastic anemia: a single-institution experience.International journal of hematology · 2025Article
- Dose-dependent effects of eltrombopag iron chelation on platelet formation.Blood vessels, thrombosis & hemostasis · 2025Article
- Efficacy of therapeutic strategies on thrombocytopenia after hematopoietic stem cell transplantation-an evidence-based meta-analysis.Therapeutic advances in hematology · 2025Article
- Expansion effect of romiplostim on hematopoietic stem and progenitor cells versus thrombopoietin and eltrombopag.International journal of hematology · 2024Article
- [Efficacy and safety of eltrombopag in the treatment of primary immune thrombocytopenia: real-world data from a single medical center].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Article
- An iron rheostat controls hematopoietic stem cell fate.Cell stem cell · 2024Article
- Increased iron uptake by splenic hematopoietic stem cells promotes TET2-dependent erythroid regeneration.Nature communications · 2024Article
- Rapid and sustained response to luspatercept and eltrombopag combined treatment in one case of clonal cytopenias of undetermined significance with prior failure to cyclosporin and androgen therapy: a case report.Therapeutic advances in hematology · 2024Article
- Eltrombopag can promote platelet implantation after allogeneic hematopoietic stem cell transplantation as safely and similarly to thrombopoietin.Frontiers in immunology · 2024Article
- Ciclopirox ethanolamine preserves the immature state of human HSCs by mediating intracellular iron content.Blood advances · 2023Article
- In Silico Evaluation of Coding and Non-Coding nsSNPs in the Thrombopoietin Receptor (Current issues in molecular biology · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Eltrombopag (EP), a small-molecule thrombopoietin receptor (TPO-R) agonist and potent intracellular iron chelator, has shown remarkable efficacy in stimulating sustained multilineage hematopoiesis in patients with bone marrow failure syndromes, suggesting an effect at the most immature hematopoietic stem and multipotent progenitor level. Although the functional and molecular effects of EP on megakaryopoiesis have been studied in the past, mechanistic insights into its effects on the earliest stages of hematopoiesis have been limited. We investigated the effects of EP treatment on hematopoietic stem cell (HSC) function using purified primary HSCs in separation-of-function mouse models, including a TPO-R-deficient strain, and stem cells isolated from patients undergoing TPO-R agonist treatment. Our mechanistic studies showed a stimulatory effect on stem cell self-renewal independently of TPO-R. Human and mouse HSCs responded to acute EP treatment with metabolic and gene expression alterations consistent with a reduction of intracellular labile iron pools that are essential for stem cell maintenance. Iron preloading prevented the stem cell stimulatory effects of EP. Moreover, comparative analysis of stem cells in the bone marrow of patients receiving EP showed a marked increase in the number of functional stem cells compared to patients undergoing therapy with romiplostim, another TPO-R agonist lacking an iron-chelating ability. Together, our study demonstrates that EP stimulates hematopoiesis at the stem cell level through iron chelation-mediated molecular reprogramming and indicates that labile iron pool-regulated pathways can modulate HSC function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.