title: Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome.
abstract: Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron's adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism-driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population.
authors.affiliation: Division of Hematologic Malignancies, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY;
authors.forename: Niraj
authors.initials: N
authors.lastname: Shenoy
authors.affiliation: Division of Hematologic Malignancies, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY;
authors.forename: Nishanth
authors.initials: N
authors.lastname: Vallumsetla
authors.affiliation: Hematology Department, Edith Wolfson Medical Center, Holon, Israel; and.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Rachmilewitz
authors.affiliation: Division of Hematologic Malignancies, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY;
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
authors.affiliation: Erythropoiesis Laboratory, New York Blood Center, New York, NY.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Ginzburg
mesh_terms: D015913:Chelation Therapy; D017707:Erythrocyte Transfusion / Q000009:adverse effects; D004912:Erythrocytes / Q000378:metabolism; D004920:Erythropoiesis; D064451:Hepcidins / Q000097:blood; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D008954:Models, Biological; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000150:complications* / Q000628:therapy*; D012307:Risk Factors
chemical_list: D064451:Hepcidins; D007502:Iron Chelating Agents; D007501:Iron