Of note, this fascinating and pleiotropic biomarker has been consistently associated also to cardiovascular diseases in recent studies, an issue that might merit further consideration in the future within the specific context of MDS. Nevertheless, GDF-15 was not correlated at all with hepcidin levels in our series. The apparent discrepancy of our results with those of Tanno and coworkers in thalassemia may be explained in terms of absolute levels. Indeed, the GDF-15 levels reported in thalassemic patients are consistently higher than those found in our MDS series, and in vitro studies have shown that significant hepcidin suppression requires very high levels, i.e. no less than 5,000 pg/ ml, being still incomplete at the highest dose of 100,000 pg/ml. Recent expression studies in erythroblasts have shown that erythroid regulation of hepcidin may be an heterogeneous phenomenon mediated by other molecules, i.e. TWSG1 for which serum assay is not yet available. Further studies are needed to clarify which mediators may play a role in hepcidin suppression at least in Doxorubicin certain MDS subtypes, particularly in RARS. The observation that iron biochemical parameters are significantly higher than in controls also in our subset of non transfused patients, also reported by others is a further argument in favour of a certain degree of iron hyperabsorption in MDS. Our study suffers of several limitations that need to be acknowledged. First, our considerations on hepcidin regulation by iron rely on ferritin levels, which are known to be an imperfect marker of iron stores. Other measures of body iron stores such as liver iron content through Magnetic Resonance may be more accurate, considering that the “gold standard” represented by liver biopsy is clearly unfeasible in thrombocytopenic and generally elderly patients with several comorbidities like those with MDS. Nevertheless, recent data by Armand and colleagues indicate that serum ferritin is still an acceptable marker of iron stores in MDS, since it showed a strong and significant correlation with estimated LIC by MR. Similarly, although our hepcidin assay is specific for the 25-mer bioactive isoform and has been clinically validated in other settings, we have to recognize that we still lack a gold standard for measuring this hormone in biological fluids. Finally, the effect of inflammatory cytokines, which may play a prominent role in certain MDS subtypes with excess myeloblast activation, could be studied only indirectly, through a surrogate like CRP.