Schematic representation of the pathogenic mechanisms of CDAII at the systemic level. The pathogenic mechanism of CDAII at a systemic level, highlighting the role of erythroferrone (ERFE) in the interplay between the bone marrow and hepatic compartments. At the bone marrow level, block of erythroid maturation results in accumulation of erythroblasts that secrete ERFE. The increased levels of ERFE are responsible for the suppression of Hamp expression, which codes for hepcidin, and this can result in liver iron overload. EPO, erythropoietin; TGF-β, transforming growth factor-β.