Iron chelation and its effect on hematopoiesis
Iron chelation is useful to ameliorate iron-related organ dysfunction, but hereditary hemochromatosis is not notorious for causing bone marrow dysfunction, and patients with beta-thalassemia and transfusional iron overload are not at risk of developing MDS or acute myeloid leukemia (AML): is iron overload irrelevant for bone marrow function?
“Part of the iron-related marrow toxicity may be due to genomic damage,” explained Professor Norbert Gattermann (Universitätsklinikum Düsseldorf, Germany) in a Hematology-in-Focus session. A mouse model showed that iron is mutagenic in hematopoietic cells through increased intracellular reactive oxygen species (ROS).
“In the context of genomic instability this may promote clonal evolution and thus accelerate progression of MDS to AML.” The KALLISTO phase IIstudy showed that iron chelator deferasirox could be employed early in the course of MDS, before the development of significant iron overload.