Non-transferrin-bound iron in myelodysplastic syndromes: a marker of ineffective erythropoiesis?

Iron overload is usually observed in patients (even untransfused) with myelodysplastic syndromes (MDS), and contributes towards the generation of low molecular weight iron complexes or non-transferrin-bound iron (NTBI), which in turn favors oxidative DNA damage and consequent apoptosis. Levels of NTBI and lipid peroxidation were evaluated by means of free serum malondyaldehyde (MDA) in untransfused MDS patients and we tried to correlate them with ineffective erythropoiesis, apoptosis and the pattern of in vitro growth. NTBI levels were found to be significantly higher in low-risk than in high-risk MDS patients, as well as in patients with a lower myeloid/erythroid ratio. MDA was found to be uniformly higher in the MDS patients as a whole than in normal controls. The bone marrow progenitor cells in the MDS patients with high NTBI levels showed a higher degree of apoptosis, but this difference was not statistically significant. Patients with a leukemic growth pattern had lower NTBI levels than those with a non-leukemic pattern. These data suggest that NTBI is related to the degree of ineffective erythropoiesis and that it contributes towards inducing apoptosis in MDS bone marrow precursors. The presence of leukemic growth is associated with low NTBI levels, probably due to increased iron consumption by blast cells.