ArticleThe Journal of clinical investigation2022
Eltrombopag inhibits TET dioxygenase to contribute to hematopoietic stem cell expansion in aplastic anemia.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed, 31 citations in OpenAlex.
- CHIP ahoy: charting a decade of discovery in clonal hematopoiesis.Haematologica · 2026Review
- Exosomes-loaded with traditional Chinese medicine constituents: a novel therapeutic avenue for aplastic anemia.Chinese medicine · 2026Review
- Iron and the immune system.Nature reviews. Immunology · 2025Review
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Advancing TET Inhibitor Development: From Structural Insights to Biological Evaluation.ACS medicinal chemistry letters · 2025Article
- Dose-dependent effects of eltrombopag iron chelation on platelet formation.Blood vessels, thrombosis & hemostasis · 2025Article
- PNPO-Mediated Oxidation of DVL3 Promotes Multiple Myeloma Malignancy and Osteoclastogenesis by Activating the Wnt/β-Catenin Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cancer treatment-induced thrombocytopenia: diagnosis, mechanisms and management.Frontiers in immunology · 2025Review
- Unravelling the role of TET2 in venous thromboembolism: insights into mechanisms and therapeutic implications.Frontiers in cardiovascular medicine · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- TET2 mutation as prototypic clonal hematopoiesis lesion.Seminars in hematology · 2024Review
- All Roads Lead to Interferon-γ: From Known to Untraveled Pathways in Acquired Aplastic Anemia.Medicina (Kaunas, Lithuania) · 2023Review
- Article
- Eltrombopag Preserves the Clonogenic Potential of Hematopoietic Stem Cells During Treatment With Antithymocyte Globulin in Patients With Aplastic Anemia.HemaSphere · 2023Article
- Clonal Hematopoiesis: Updates and Implications at the Solid Tumor-Immune Interface.JCO precision oncology · 2023Review
- New Insights into Hematopoietic Stem Cell Expansion to Stimulate Repopulation of the Adult Blood System for Transplantation.Life (Basel, Switzerland) · 2022Review
- Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Eltrombopag, an FDA-approved non-peptidyl thrombopoietin receptor agonist, is clinically used for the treatment of aplastic anemia, a disease characterized by hematopoietic stem cell failure and pancytopenia, to improve platelet counts and stem cell function. Eltrombopag treatment results in a durable trilineage hematopoietic expansion in patients. Some of the eltrombopag hematopoietic activity has been attributed to its off-target effects, including iron chelation properties. However, the mechanism of action for its full spectrum of clinical effects is still poorly understood. Here, we report that eltrombopag bound to the TET2 catalytic domain and inhibited its dioxygenase activity, which was independent of its role as an iron chelator. The DNA demethylating enzyme TET2, essential for hematopoietic stem cell differentiation and lineage commitment, is frequently mutated in myeloid malignancies. Eltrombopag treatment expanded TET2-proficient normal hematopoietic stem and progenitor cells, in part because of its ability to mimic loss of TET2 with simultaneous thrombopoietin receptor activation. On the contrary, TET inhibition in TET2 mutant malignant myeloid cells prevented neoplastic clonal evolution in vitro and in vivo. This mechanism of action may offer a restorative therapeutic index and provide a scientific rationale to treat selected patients with TET2 mutant-associated or TET deficiency-associated myeloid malignancies.
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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.