Transferrin receptor 2 is a potential novel therapeutic target for β-thalassemia: evidence from a murine model
Open accessAbstract
β-thalassemias are genetic disorders characterized by anemia, ineffective erythropoiesis, and iron overload. Current treatment of severe cases is based on blood transfusion and iron chelation or allogeneic bone marrow (BM) transplantation. Novel approaches are explored for nontransfusion-dependent patients (thalassemia intermedia) who develop anemia and iron overload. Here, we investigated the erythropoietin (EPO) receptor partner, transferrin receptor 2 (TFR2), as a novel potential therapeutic target. We generated a murine model of thalassemia intermedia specifically lacking BM Tfr2: because their erythroid cells are more susceptible to EPO stimulation, mice show improved erythropoiesis and red blood cell morphology as well as partial correction of anemia and iron overload. The beneficial effects become attenuated over time, possibly due to insufficient iron availability to sustain the enhanced erythropoiesis. Germ line deletion of Tfr2, including haploinsufficiency, had a similar effect in the thalassemic model. Because targeting TFR2 enhances EPO-mediated effects exclusively in cells expressing both receptors, this approach may have advantages over erythropoiesis-stimulating agents in the treatment of other anemias.
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Selective inactivation of bone marrow Tfr2 improves anemia in a non-transfusion-dependent Hbbth3/+ model, enhancing the sensitivity of erythroid cells to erythropoietin.
“Selective inactivation of bone marrow Tfr2 improves anemia in a non-transfusion-dependent Hbbth3/+ model, enhancing the sensitivity of erythroid cells to ery-thropoietin.126”
From Iron metabolism and iron disorders revisited in the hepcidin era (2020) · cites this paper as [126]
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Iron metabolism and iron disorders revisited in the hepcidin era
Camaschella, C., Nai, A., & Silvestri, L. (2020) · Haematologica · doi:10.3324/haematol.2019.232124 · Cited by 734 · see citing works
Self-citation
- Authors
- Artuso, I., Lidonnici, M. R., Altamura, S., Mandelli, G., Pettinato, M., Muckenthaler, M. U., Silvestri, L., Ferrari, G., Camaschella, C., & Nai, A.
- Affiliations
- IRCCS Ospedale San Raffaele (IT)
- Vita-Salute San Raffaele University (IT)
- Heidelberg University (DE)
- The San Raffaele Telethon Institute for Gene Therapy (IT)
- Corresponding author
- Artuso, Irene
- Lidonnici, Maria Rosa
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2018-11-22
- Volume
- 132
- Issue
- 21
- Pages
- 2286-2297
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC6302281
- OpenAlex
- W2890188806
- Cited by
- 38
- References
- 9
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 2
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Update notices
- erratum (2019-07-04)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- European Hematology Association
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- transferrin receptor 2, beta-thalassemia, thalassemia intermedia, erythropoietin receptor, erythropoiesis, iron overload, anemia, haploinsufficiency, erythroid cells, therapeutic target
- MeSH terms
- Anemia, Animals, Cells, Cultured, Disease Models, Animal, Erythropoiesis, Erythropoietin, Female, Male, Mice, Inbred C57BL, Receptors, Transferrin, Genetic Therapy, beta-Thalassemia, Gene Deletion, Iron Overload, Erythroid Cells
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