Myelodysplastic Syndromes
Myelodysplastic syndromes are clonal hematopoietic disorders with ineffective hematopoiesis in bone marrow and cytopenia in peripheral blood. For those living with these disorders, excessive iron commonly develops, driven both by repeated transfusions of red blood cells and by the body's own impaired blood-making processes. As a premier research service provider focused on iron metabolism, Protheragen strives to equip scientists and research teams around the globe with integrated, end-to-end services tailored to iron-related pathologies, including myelodysplastic syndromes.
Overview of Myelodysplastic Syndromes
Myelodysplastic syndromes are clonal hematologic neoplasms distinguished by defective hematopoietic stem cell (HSC) differentiation and by ineffective hematopoiesis in the bone marrow. In the US, their incidence is about 4 in 100,000 per year, and in Europe may be even double. Increased iron in the body is a marked feature in the course of myelodysplastic syndromes and is involved in the achievement of therapy and individual survival. Failure to use iron secondary to poor erythropoiesis and to chronic transfusion therapy in individuals with myelodysplastic syndromes results in iron overload, which correlates with inferior outcomes.
Fig.1 Iron chelation therapy in myelodysplastic syndromes. (Hoff, F. W., et al., 2025)
Iron Metabolism Abnormalities in Myelodysplastic Syndromes
Individuals diagnosed with myelodysplastic syndromes characterized by ring sideroblasts (MDS-RS) frequently develop iron overload, and almost all carry mutations in the splicing factor 3B subunit 1 (SF3B1). These SF3B1 mutations appear to promote ring sideroblast formation partly by reducing the expression of ATP-binding cassette subfamily B member 7, thereby impairing the mitochondrial export of iron-sulfur clusters to the cytoplasm. Hepatic dysfunction, cardiac failure, atherosclerosis, and diabetes occur due to iron overload, also in myelodysplastic syndromes, and excess iron may inhibit normal hematopoiesis.
Fig.2 Iron overload in myelodysplastic syndrome individuals. (Lyle, L., and Hirose, A., 2018)
Besides this, dysplastic erythroblast in myelodysplastic syndromes releases humoral factors (e.g., erythroferrone) that inhibit hepatic hepcidin production. Hepcidin is the central regulator of systemic iron homeostasis, and hepcidin suppression causes increased iron absorption in the gut, contributing to systemic iron overload.
Therapeutics Development for Myelodysplastic Syndromes
| Drug Name | Mechanism of Action | Targets | NCT Number | Research Phase |
| Deferiprone | An oral iron chelator functions by binding excess iron in the body, forming a complex, and facilitating its excretion, thereby lowering iron overload. | Iron overload | NCT02477631 | Phase II |
| Deferasirox | An iron chelator that binds excess iron to mitigate iron overload. | Iron overload | NCT03387475 | Phase II |
| Luspatercept | Binds to selective TGF-β superfamily ligands, which facilitates the maturation of red blood cells and resolves the ineffective erythropoiesis scenario, hence alleviating anemia. | TGF-β | NCT07096297 | Phase II |
| CAR-NK cell | Specifically identify and eliminate the malignant cells within the bone marrow of individuals with myelodysplastic syndromes. | CD70, IL15R | NCT05092451 | Phase I/II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.
Our Services
Protheragen provides an end-to-end service to support your drug development advancements, from early target identification to preclinical validation. We offer diagnostic, therapeutic, and disease model development services, and are a bridge between basic research and application, helping the transition from the bench to the bed to bring promising discoveries to effective therapies.
Therapeutic Development Services
- Small Molecule Drug Development
- Gene Therapy Development
- Therapeutic Peptide Development
- Cell Therapy Development
- Therapeutic Antibody Development
- Therapeutic Protein Development
Animal Model Development Services for Myelodysplastic Syndromes
Preclinical animal models play an irreplaceable role in understanding disease mechanisms, preclinical trials of new therapy methods, and the prediction of outcomes of therapeutic interventions. We provide tailored animal-modeling services for myelodysplastic syndromes.
| Genetically Engineered Model | |
| These models entail targeted alterations of the murine genome to precisely create particular genetic mutations and disease phenotypes present in myelodysplastic syndromes. | |
| Optional models | NHD13 transgenic model, etc. |
| Induced Animal Model | |
| Induced models of animal models are generally established by the therapy of animals with chemicals or radiation to induce myelodysplastic syndromes-like features in vivo. | |
| Optional models | Benzene-induced model, Alkylation reagent induction model, Radiation-induced model, Dimethylbenzanthracene (DMBA) induced model, etc. |
| Xenograft Model | |
| Xenograft models involve the transplantation of human myelodysplastic syndrome cells (e.g., patients' cells or MDS cell lines) into an immunodeficient mouse. | |
| Optional models | Patient-derived xenograft (PDX) models, Cell line-derived xenograft (CDX) models, etc. |
Pharmacokinetics and Drug Safety Evaluation Services
By taking advantage of our expertise in myelodysplastic syndromes pathobiology and in iron metabolism, Protheragen helps drive the discovery and the validation of attractive drug candidates for myelodysplastic syndromes, as well as provide preclinical pharmacokinetic and drug safety services. Ready to take your myelodysplastic syndromes investigations to the next level? Get in touch with us today to find out how our bespoke services can help your pioneering approach.
References
- Lyle, Lindsey, and Alex Hirose. "Iron Overload in Myelodysplastic Syndromes: Pathophysiology, Consequences, Diagnosis, and Treatment." Journal of the advanced practitioner in oncology 9.4 (2018): 392-405.
- Słomka, Artur et al. "The Role of Hepcidin in Myelodysplastic Syndromes (MDS): A Systematic Review of Observational Studies." Cancers 16.2 (2024): 332.
- Hoff, Fieke W et al. "Iron chelation therapy in myelodysplastic syndromes and allogeneic hematopoietic cell transplantation, a delicate balance." Blood reviews (2025): 101319.