Iron Overload-Induced Oxidative Stress in Myelodysplastic Syndromes and its Cellular Sequelae, Cecilia Kim, UG '23 (2289803)
The myelodysplastic syndromes (MDS) are a group of blood disorders that lead to improper blood cell formation and anemia. As a result, MDS patients often require red blood cell transfusions, which contain high levels of iron. Since the body has no mechanism to excrete excess iron, frequent transfusions may result in iron overload (IOL), or an excess amount of iron in patients. In IOL, the binding sites on the transferrin proteins that are responsible for iron transport are saturated and non-transferrin bound iron reacts by Fenton chemistry to increase the production of reactive oxygen species (ROS), which can be toxic to cells and tissues. We reviewed preclinical and clinical evidence on oxidative stress from ROS formed by IOL in MDS in order to investigate their potential relevance to MDS pathology. We illustrated how IOL-induced ROS in the heart, liver, and bone marrow can damage proteins and DNA, cause cell and organelle death, impair signaling pathways, and lead to increased organ damage. We concluded that it is possible that transfusions meant to treat MDS patients of improper blood cell formation may lead to other adverse clinical outcomes by causing IOL. For future directions, we suggest that investigating methods to reduce iron levels by iron chelation therapy to trap and remove excess iron, or finding ways to mitigate the damage from ROS species using antioxidants in a clinical setting will be helpful in finding therapies for MDS to promote patient health and quality of life.