Iron Overload Management in Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are clonal disorders of haematopoietic stem cells characterised by ineffective blood cell production, peripheral cytopenias and a risk of progression to acute leukaemia. Recurrent red blood cell transfusions and intrinsic dysregulation of iron metabolism frequently lead to systemic iron overload, which exacerbates oxidative stress, impairs bone marrow function and contributes to organ toxicity. Management strategies focus on reducing iron burden and mitigating its deleterious effects through pharmacological chelation, hormonal modulation of iron homeostasis and emerging approaches that exploit iron-dependent cell death pathways. By combining established chelators with novel agents targeting reactive oxygen species (ROS), lipid peroxidation and key regulatory proteins, contemporary research aims to refine personalised regimens that preserve marrow function, delay disease progression and improve quality of life.

Research from Nature Portfolio

A foundational study in a murine model revealed that iron overload markedly impairs haematopoietic stem and progenitor cell function by elevating ROS levels via activation of NOX4 and p38MAPK. This oxidative injury induces mitochondrial dysfunction and reduces long-term engraftment capacity. Importantly, both iron chelation and antioxidant intervention restored cellular viability and clonogenic potential, demonstrating the therapeutic value of concurrently targeting iron accumulation and ROS signalling. These insights have underpinned translational efforts to integrate chelation with redox-modulating strategies in MDS management.

Iron Overload Management in Myelodysplastic Syndromes publication trend

The graph below shows the total number of articles in iron overload management in myelodysplastic syndromes across all publications each year (not limited to Nature Index journals).

Technical terms

Myelodysplastic syndromes (MDS): A heterogeneous group of clonal bone marrow disorders with ineffective haematopoiesis and risk of leukaemic transformation.

Iron chelation therapy: Use of small-molecule agents to bind and remove excess systemic iron, limiting tissue deposition and oxidative damage.

Ferroptosis: Iron-dependent regulated cell death characterised by lipid peroxidation and depletion of glutathione.

Reactive oxygen species (ROS): Highly reactive oxygen-containing molecules that can damage proteins, lipids and DNA when not adequately neutralised.

Hepcidin: Hepatic peptide hormone that controls systemic iron levels by inhibiting intestinal absorption and macrophage iron release.

Non-transferrin-bound iron (NTBI): Circulating iron not bound to transferrin, capable of catalysing the formation of harmful free radicals.

References

1. ROS-mediated iron overload injures the hematopoiesis of bone marrow by damaging hematopoietic stem/progenitor cells in mice. Scientific Reports (2015).
2. Abnormal Ferroptosis in Myelodysplastic Syndrome. Frontiers in Oncology (2020).
3. The Clinical Significance of Iron Overload and Iron Metabolism in Myelodysplastic Syndrome and Acute Myeloid Leukemia. Frontiers in Immunology (2021).