title: Hepcidin levels and their determinants in different types of myelodysplastic syndromes.
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.
authors: Hematology Unit, AOU Careggi, University of Florence, Florence, Italy.
authors: Valeria
authors: V
authors: Santini
authors: Domenico
authors: D
authors: Girelli
authors: Alessandro
authors: A
authors: Sanna
authors: Nicola
authors: N
authors: Martinelli
authors: Lorena
authors: L
authors: Duca
authors: Natascia
authors: N
authors: Campostrini
authors: Agostino
authors: A
authors: Cortelezzi
authors: Michela
authors: M
authors: Corbella
authors: Alberto
authors: A
authors: Bosi
authors: Gianluigi
authors: G
authors: Reda
authors: Oliviero
authors: O
authors: Olivieri
authors: Maria Domenica
authors: MD
authors: Cappellini
mesh_terms: D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D001803:Blood Transfusion; D016022:Case-Control Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000097:blood; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000145:classification*; D012016:Reference Values; D014944:World Health Organization
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D005293:Ferritins; D007501:Iron