The bone marrow hematopoietic microenvironment is impaired in iron‐overloaded mice

Abstract

Iron-overloaded (IO) mice did not show significant defects in the hematopoietic data of the peripheral blood. Myeloid progenitor cells in the bone marrow were increased in IO mice, but the number and function of the erythroid progenitors and hematopoietic stem cells were not significantly affected. However, bone marrow transplantation from normal donors to IO recipients showed delayed hematopoietic reconstitution, which indicates that excess iron impacts the hematopoietic microenvironment negatively. Microarray and quantitative RT-PCR analyses on the bone marrow stromal cells demonstrated remarkably reduced expression of CXCL12, VCAM-1, Kit-ligand, and IGF-1 in the iron-overloaded mice. In addition, erythropoietin and thrombopoietin levels were significantly suppressed, and increased oxidative stress was observed in the IO bone marrow and liver. Consequently, our findings indicate that excess iron can damage bone marrow stromal cells and other vital organs, disrupting hematopoiesis presumably by increased oxidative stress.

Iron overload in myelodysplastic syndromes (MDS)

“…Iron overload also caused stromal dysfunction in a mouse model [12]. BM transplantation from normal donor mice to IOL recipients resulted in delayed hematopoietic reconstitution, indicating that excess iron disturbed the hematopoietic microenvironment.…”

“…Figure 3 illustrates where IOL may have an aggravating effect on MDS pathophysiology. Experimental evidence indicates that IOL contributes to stromal dysfunction [12,13] and exacerbates genomic instability, thereby hastening clonal evolution towards leukemia.…”

Transfusion Independency and Histological Remission in a Patient with Advanced Primary Myelofibrosis Receiving Iron-Chelation Therapy with Deferasirox

“…Erythroid colony assays were significantly lower in patients with a ferritin > 2.500 ng/ml than in patients with normal ferritin levels [4]. Erythropoietin and thrombopoietin levels were also suppressed, and increased oxidative stress in the bone marrow was observed [18,19]. Another study in transfusion-dependent MDS patients suggested that oxidative stress due to iron overload could cause DNA damage and, therefore, contribute to the MDS development [20].…”

Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation

“…The levels of erythropoietin and thrombopoietin were significantly low in iron-overloaded mice compared to the normal group. The authors concluded that excess iron disrupts the hematopoietic microenvironment [19]. Zhang et al evaluated the effect of iron overload on the bone marrow microenvironment in mice and found that chemokine stromal cell-derived factor-1, stem cell factor-1, and vascular endothelial growth factor-1 expressions were decreased.…”