Recent advances in the understanding of iron overload in sideroblastic myelodysplastic syndrome

Br J Haematol. 2010 May;149(3):322-33. doi: 10.1111/j.1365-2141.2009.08051.x. Epub 2010 Jan 11.

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic stem cell malignancies. A subgroup, the so-called sideroblastic MDS, shows ring sideroblasts in the bone marrow aspirate that represent mitochondrial iron accumulation. Patients with sideroblastic MDS also develop systemic iron overload and generally have a low-risk MDS. Therefore it is important to understand the mechanisms responsible for iron accumulation and the associated toxicity in these patients. Recently, low levels of the iron-regulatory peptide hepcidin were found to contribute to body iron overload in beta-thalassaemia patients. A similar mechanism may account for systemic iron accumulation in sideroblastic MDS. Mitochondrial iron accumulation is observed in several subtypes of MDS, and predominantly in refractory anaemia with ring sideroblasts. The presence of ring sideroblasts is also the diagnostic hallmark in patients with inherited forms of sideroblastic anaemia. The ever-increasing insights into the affected pathways in inherited sideroblastic anaemia may lead to a better comprehension of the pathogenesis of mitochondrial iron accumulation in MDS patients. Overall, an improved understanding of the mechanisms responsible for iron overload in MDS will lead to novel treatment strategies to reduce both systemic and mitochondrial iron overload, resulting in less tissue damage and more effective erythropoiesis.

Publication types

  • Review

MeSH terms

  • Anemia, Sideroblastic / complications
  • Anemia, Sideroblastic / metabolism
  • Humans
  • Iron Chelating Agents / therapeutic use
  • Iron Overload / drug therapy
  • Iron Overload / etiology*
  • Iron Overload / metabolism
  • Mitochondria / metabolism
  • Myelodysplastic Syndromes / complications*
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / metabolism

Substances

  • Iron Chelating Agents