ArticleFrontiers in immunology2025
Iron overload promotes myeloid differentiation of normal hematopoietic stem cells and educates macrophage mediated immunosuppression in acute myeloid leukemia.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- From gut-reproductive microbiota to ferroptosis: a comprehensive insight into the molecular-pathogenicity of endometriosis.Frontiers in immunology · 2026Review
- Iron homeostasis and macrophage polarization in pulmonary fibrosis: mechanisms and therapeutic perspectives.Frontiers in immunology · 2025Review
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12 authors.
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Abstract
Background: The hematopoietic ecosystem comprises both cellular components such as hematopoietic stem cells (HSCs) and immune cells as well as non-cellular components including iron. Systemic iron overload, which leads to serious complications and affects both patients' quality of life and overall survival, is a common clinical challenge in patients with acute myeloid leukemia (AML). We previously elucidated the direct effects of iron overload on AML cells. It's worth noting that iron overload remodels the hematopoietic ecosystem. However, whether and how remodeled leukemic microenvironment with overloaded iron regulates normal HSCs and immune cells, especially leukemia-associated macrophages (LAMs), in AML have not been elucidated. Methods: The MLL-AF9-induced AML (MA9) cells were originated from c-kit Results: Iron overload skewed myeloid differentiation of normal HSCs. Furthermore, iron overload affected LAMs in the AML microenvironment by promoting LAM polarization toward an M2 phenotype. Functionally, iron overload decreased the phagocytic function of LAMs against leukemia cells and inhibited LAM-induced T cell activation by acquiring a tolerogenic phenotype with aberrant immune checkpoints. Moreover, depletion of LAMs attenuated iron overload caused acceleration of AML progression. Conclusions: Collectively, this study reveals the significance of iron overload in remodeling hematopoietic ecosystem and affecting HSC and LAM function in AML, providing new insights into the multifaceted role of iron overload in leukemia.
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