Hepcidin Levels and Their Determinants in Different Types of Myelodysplastic Syndromes 英文参考文献.docVIP

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Hepcidin Levels and Their Determinants in Different Types of Myelodysplastic Syndromes 英文参考文献.doc

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Hepcidin Levels and Their Determinants in Different Types of Myelodysplastic Syndromes 英文参考文献

HepcidinLevelsandTheirDeterminantsinDifferent TypesofMyelodysplasticSyndromes ValeriaSantini1.,DomenicoGirelli2*.,AlessandroSanna1,NicolaMartinelli2,LorenaDuca3 ,Natascia Campostrini2,AgostinoCortelezzi4,MichelaCorbella2,AlbertoBosi1,GianluigiReda4,OlivieroOlivieri2, MariaDomenicaCappellini3 1Hematology Unit, AOU Careggi, University of Florence, Florence, Italy, 2Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy, 3DepartmentofInternalMedicine,‘‘Ca` Granda’’FoundationIRCCS,UniversityofMilan,Milan,Italy,4HematologyUnit1,‘‘Ca` Granda’’FoundationIRCCS,Universityof Milan,Milan,Italy Abstract IronoverloadmayrepresentanadditionalclinicalprobleminpatientswithMyelodysplasticSyndromes(MDS),withrecent data suggesting prognostic implications. Beyond red blood cells transfusions, dysregulation of hepcidin, the key iron hormone,mayplayarole,butstudiesuntilnowhavebeenhamperedbytechnicalproblems.Usingarecentlyvalidated assay,wemeasuredserumhepcidinin113patientswithdifferentMDSsubtypes.Meanhepcidinlevelswereconsistently heterogeneousacrossdifferentMDSsubtypes,withthelowestlevelsinrefractoryanemiawithringedsideroblasts(RARS, 1.43nM)andthehighestinrefractoryanemiawithexcessblasts(RAEB,11.3nM)orinchronicmyelomonocyticleukemia (CMML,10.04nM)(P=0.003byANOVA).MDSsubtypesremainedsignificantpredictorsofhepcidininmultivariateanalyses adjusted for ferritin and transfusion history. Consistently with current knowledge on hepcidin action/regulation, RARS patientshadthehighestlevelsoftoxicnon-transferrin-bound-iron,whileRAEBandCMMLpatientshadsubstantialelevation of C-Reactive Protein as compared to other MDS subtypes, and showed lost of homeostatic regulation by iron. Growth differentiationfactor15didnotappearasaprimaryhepcidinregulatorinthisseries.Ifconfirmed,theseresultsmayhelpto calibratefuturetreatmentswithchelatingagentsand/orhepcidinmodulatorsinMDSpatients. Citation: Santini V, Girelli D, Sanna A, Martinelli N, Duca L, et al. (2011) Hepcidin