Myelodysplastic syndrome macrophages have aberrant iron storage and heme oxygenase-1 expression

Abstract

Iron overload and transfusion dependance portend poor risk in myelodysplastic syndromes (MDS); bone marrow macrophages store iron and limit oxidative damage through heme oxygenase-1 (HO1). We assessed iron stores and macrophage HO1 expression in MDS using image analysis of intact diagnostic bone marrow biopsies and qualitative scoring of marrow aspirate iron among 129 cytopenic patients, 67 with MDS and 62 similarly aged patients with benign cytopenias. Using double immunofluorescence and sequential iron and immunohistochemistry staining, we showed that marrow iron colocalizes with HO1 and H-ferritin to CD163 + macrophages. Marrow iron was elevated in MDS independent of transfusion status, a finding of potential utility in distinguishing benign cytopenia from MDS. Among MDS patients only, CD163 + macrophage density and HO1 and H-ferritin expression by CD163 + macrophages increased in tandem with marrow iron. High HO1 was significantly associated with shorter overall survival among MDS patients independent of IPSSR and history of transfusion.

Keywords:

• Heme oxygenase
• iron
• macrophage
• myelodysplastic syndromes

Acknowledgements

The authors gratefully acknowledge departmental support by the Department of Pathology, Stanford University School of Medicine. TMAs were previously constructed with support from Veteran’s Affairs Career Development Award-2 to DG.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.3109/10428194.2015.1121259.