AM25-ST-17-L - Novel Insights into Iron Toxicities in Hematologic Diseases and Related Pharmacological and Gene Therapy Approaches

Proposed Session Description: Patients with thalassemias (THAL), sickle cell disease (SCD), X-linked sideroblastic anemia, hereditary spherocytosis, and myelodysplastic syndromes (MDS) are prone to develop iron overload due to ineffective/defective erythropoiesis and chronic transfusion therapy, which is often required to correct the underlying anemia. This session will highlight the molecular mechanisms driving iron overload in these hematologic diseases and provide novel insights on how iron contributes to disease pathophysiology. Iron-triggered cellular and molecular mechanisms aggravating THAL and MDS pathophysiology will be discussed.
Importantly, this session will address novel therapeutic approaches, including iron restriction drugs, erythroid maturation agents, and gene therapy approaches, in correcting iron overload and ameliorating disease pathophysiology. The implication of iron restriction in improving erythropoiesis in both THAL and MDS, as well as in preserving the stem cell pool, limiting myeloid expansion, and delaying leukemic transformation in MDS will be shown. The superior effect of combining iron restriction agent and erythroid maturation drugs (eg. luspatercept) for the improvement of erythropoiesis in THAL and MDS will be highlighted. Ultimately, ex vivo and novel in vivo nanoparticle-based system for the systemic delivery of gene therapies to blood stem cell and their potential to improve hematologic diseases will be presented.