[Impacts of iron overload on hematopoiesis and its microenvironment]

A significant number of reports have described hematopoietic improvement after iron chelation therapy in iron-overloaded (IO) patients. These observations indicate negative impacts of excess iron on hematopoiesis. To investigate how excess iron affects hematopoiesis, we generated IO mice and examined hematopoietic parameters in these mice. IO mice did not show significant defects in the hematopoietic data of 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. Quantitative RT-PCR analyses of the bone marrow stromal cells demonstrated remarkably reduced expressions of several important cytokines, e.g. CXCL12, VCAM-1, Kit-ligand and IGF-1, in the IO mice. In addition, erythropoietin and thrombopoietin levels were significantly suppressed, and oxidative stress was significantly increased in the IO bone marrow and liver. Our findings thus indicate that excess iron can damage bone marrow stromal cells and other vital organs that support hematopoiesis, presumably via increased oxidative stress.