Oxidative Stress in β-Thalassemia, Myelodysplastic Syndrome, and Acute Leukemia

β-Thalassemia, myelodysplastic syndrome, and acute myeloid leukemia are diseases profoundly different in etiopathogenesis and outcome but are all characterized by ineffective erythropoiesis, iron overload, and iron-related toxicity, which lead to cellular oxidative stress and organ damages. In many patients, excess iron may contribute to inadequate reactive oxidative species (ROS) homeostasis and the genomic instability. Moreover, when intracellular ROS production exceeds the protective antioxidant enzyme systems, an intracellular oxidative stress state is established. This biochemical model seems to be at the basis of liver, heart, and endocrine gland tissue damage in thalassemic and leukemic disease. Nevertheless, it has only recently been considered that bone marrow, and consequently hemopoiesis, could be another important target for iron-mediated damage, in particular in the process of leukemogenesis. The main hypothesis is that cytotoxicity is not merely and directly caused by stored iron but by an abnormality of the dynamic balance between the iron stored in the body and the iron used in biological processes. It would appear sufficient to cause an alteration in the balance at cellular level to trigger the induction of intracellular oxidative stress, which leads to cytotoxicity and cell death.