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. 2011;6(8):e23109.
doi: 10.1371/journal.pone.0023109. Epub 2011 Aug 19.

Hepcidin levels and their determinants in different types of myelodysplastic syndromes

Valeria Santini  1 , Domenico Girelli, Alessandro Sanna, Nicola Martinelli, Lorena Duca, Natascia Campostrini, Agostino Cortelezzi, Michela Corbella, Alberto Bosi, Gianluigi Reda, Oliviero Olivieri, Maria Domenica Cappellini
Affiliations

Hepcidin levels and their determinants in different types of myelodysplastic syndromes

Valeria Santini et al. PLoS One. 2011.

Abstract

Iron overload may represent an additional clinical problem in patients with Myelodysplastic Syndromes (MDS), with recent data suggesting prognostic implications. Beyond red blood cells transfusions, dysregulation of hepcidin, the key iron hormone, may play a role, but studies until now have been hampered by technical problems. Using a recently validated assay, we measured serum hepcidin in 113 patients with different MDS subtypes. Mean hepcidin levels were consistently heterogeneous across different MDS subtypes, with the lowest levels in refractory anemia with ringed sideroblasts (RARS, 1.43 nM) and the highest in refractory anemia with excess blasts (RAEB, 11.3 nM) or in chronic myelomonocytic leukemia (CMML, 10.04 nM) (P = 0.003 by ANOVA). MDS subtypes remained significant predictors of hepcidin in multivariate analyses adjusted for ferritin and transfusion history. Consistently with current knowledge on hepcidin action/regulation, RARS patients had the highest levels of toxic non-transferrin-bound-iron, while RAEB and CMML patients had substantial elevation of C-Reactive Protein as compared to other MDS subtypes, and showed lost of homeostatic regulation by iron. Growth differentiation factor 15 did not appear as a primary hepcidin regulator in this series. If confirmed, these results may help to calibrate future treatments with chelating agents and/or hepcidin modulators in MDS patients.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Correlation plot between hepcidin and serum ferritin levels (logarithmic scale).
(A) Controls versus all MDS patients. (B) MDS patients stratified according to WHO classification.
Figure 2
Figure 2. Correlation plot between serum hepcidin and serum ferritin levels in different MDS subtypes as compared to controls (logarithmic scale).
(A) Controls versus RA. (B) Controls versus 5q- syndrome and RARS. (C) Controls versus CMML and RAEB.
Figure 3
Figure 3. Proposed mechanisms controlling hepcidin production in different MDS subtypes.
See this image and copyright information in PMC

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