Review ArticleUnraveling the mechanisms behind iron overload and ineffective hematopoiesis in myelodysplastic syndromes

- MDS is associated with ineffective hematopoiesis and peripheral blood cytopenias.
- Red blood cell transfusion support can result in iron-induced toxicity.
- Accumulation of reactive oxygen species caused by iron overload worsens hematopoiesis.
- Iron chelation therapy can improve hematologic parameters and may prolong survival.
- Other potential new strategies for reducing iron overload are under investigation.

Myelodysplastic syndromes (MDS) are a group of clonally-acquired blood disorders characterized by ineffective hematopoiesis leading to cytopenias. Red blood cell transfusions are an important component of supportive care in patients with MDS. Prolonged exposure to transfusions can lead to iron overload, which results in iron-induced toxicity caused by the production of reactive oxygen species (ROS). ROS accumulation has detrimental effects also on hematopoietic stem cells and may contribute to MDS progression. The observation that iron chelation improves hematologic parameters and reduces transfusion dependence further indicates that iron overload impairs hematopoiesis. Over the past decade, the mechanisms regulating iron homeostasis and the complex interplay between iron overload and toxicity, ineffective hematopoiesis, and transformation to leukemia have become clearer. In this narrative review, we provide an overview of recent findings pertaining to iron overload in patients with MDS and its effects on hematopoiesis. We also briefly discuss the position of chelation therapy in the context of the new developments.