Iron overload impairs normal hematopoietic stem and progenitor cells through reactive oxygen species and shortens survival in myelodysplastic syndrome mice

Accumulating clinical evidence implicates a suppressive effect on hematopoiesis in myelodysplastic syndrome patients with iron overload. However, how iron overload influences hematopoiesis in myelodysplastic syndrome remains unknown. Here, the RUNX1S291fs-transduced bone marrow mononuclear cells were yielded and transplanted into lethally irradiated recipient mice together with radioprotective bone marrow cells to generate myelodysplastic syndrome mice. Eight weeks post transplantation, the recipient mice were administered intraperitoneal injection of 0.2 ml iron dextran at a concentration of 25mg/ml once every other day for 8 times to establish iron overload model. At the present study, we show that iron overload impairs the frequency and colony-forming capacity of normal hematopoietic stem and progenitor cells, especially in erythroid, in myelodysplastic syndrome mice, which at least in part, due to growth differentiation factor 11 induced reactive oxygen species and shortening survival of myelodysplastic syndrome mice. Given that we are the first to construct iron overload model in myelodysplastic syndrome mice, we hope this model will be helpful for further exploring the influence and mechanism of iron overload on myelodysplastic syndrome.