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Updated: Mar 27, 2026
Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies
Published on: November 10, 2023
Myelodysplastic syndrome macrophages have aberrant iron storage and heme oxygenase-1 expression
Grant Nybakken1,2, Dita Gratzinger1
1a Department of Pathology , Stanford University School of Medicine , Stanford , CA , USA ;
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.
Insights
Iron overload in myelodysplastic syndromes (MDS) is linked to higher heme oxygenase-1 (HO1) in bone marrow macrophages. High HO1 indicates poorer survival in MDS patients, regardless of transfusion history.
Area of Science:
- Hematology
- Oncology
- Cell Biology
Background:
- Myelodysplastic syndromes (MDS) are associated with iron overload and transfusion dependence, negatively impacting patient prognosis.
- Bone marrow macrophages play a crucial role in iron storage and mitigating oxidative stress via heme oxygenase-1 (HO1).
Purpose of the Study:
- To investigate the relationship between iron stores, macrophage HO1 expression, and clinical outcomes in patients with myelodysplastic syndromes (MDS).
- To assess the utility of marrow iron levels and macrophage HO1 expression in differentiating MDS from benign cytopenias.
Main Methods:
- Analysis of iron stores and HO1 expression in bone marrow biopsies from 129 cytopenic patients (67 MDS, 62 benign cytopenias) using image analysis and immunofluorescence staining.
- Quantitative assessment of marrow iron, CD163+ macrophage density, HO1, and H-ferritin expression.
- Correlation of findings with International Prognostic Scoring System (IPSSR) and transfusion history.
Main Results:
- Marrow iron was elevated in MDS patients irrespective of transfusion status, suggesting potential diagnostic value.
- In MDS patients, increased CD163+ macrophage density correlated with higher marrow iron, HO1, and H-ferritin levels.
- Elevated HO1 expression in CD163+ macrophages was significantly associated with shorter overall survival in MDS patients, independent of IPSSR and transfusion history.
Conclusions:
- Bone marrow iron accumulation and HO1 expression in macrophages are significant features of MDS.
- High HO1 expression in macrophages is a novel prognostic biomarker for poor survival in MDS patients.
- Assessing marrow iron and macrophage HO1 may aid in MDS diagnosis and prognostication.
