Hepcidin levels and their determinants in different types of myelodysplastic syndromes
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 ham...
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| creator | Santini, Valeria Girelli, Domenico Sanna, Alessandro Martinelli, Nicola Duca, Lorena Campostrini, Natascia Cortelezzi, Agostino Corbella, Michela Bosi, Alberto Reda, Gianluigi Olivieri, Oliviero Cappellini, Maria Domenica |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0023109 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0023109</identifier><identifier>PMID: 21886780</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Analysis ; Anemia ; Antimicrobial Cationic Peptides - blood ; Biology ; Blast cells ; Blood cells ; Blood Transfusion ; C-reactive protein ; Case-Control Studies ; Chelating agents ; Chelation ; Chromatography ; Chronic myelomonocytic leukemia ; Disorders ; Erythrocytes ; Female ; Ferritin ; Ferritins - blood ; Hematology ; Hemodialysis ; Hepcidin ; Hepcidins ; Homeostasis ; Humans ; Inflammation ; Internal medicine ; Iron ; Iron - blood ; Leukemia ; Linear Models ; Male ; Medical prognosis ; Medicine ; Metabolism ; Models, Biological ; Modulators ; Mutation ; Myelodysplastic syndrome ; Myelodysplastic syndromes ; Myelodysplastic Syndromes - blood ; Myelodysplastic Syndromes - classification ; Myelomonocytic leukemia ; Patients ; Proteins ; Red blood cells ; Reference Values ; Refractory anemia ; Scientific imaging ; Sideroblasts ; Stem cells ; Transferrin ; Transferrins ; Transfusion ; Transplants & implants ; Variance analysis ; World Health Organization</subject><ispartof>PloS one, 2011-08, Vol.6 (8), p.e23109</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Santini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Santini et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-979c10c26eefc046ebc874db0646708b898248c355bf8c4029a371cd2c1cd5143</citedby><cites>FETCH-LOGICAL-c691t-979c10c26eefc046ebc874db0646708b898248c355bf8c4029a371cd2c1cd5143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158762/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158762/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21886780$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kaufman, Dan</contributor><creatorcontrib>Santini, Valeria</creatorcontrib><creatorcontrib>Girelli, Domenico</creatorcontrib><creatorcontrib>Sanna, Alessandro</creatorcontrib><creatorcontrib>Martinelli, Nicola</creatorcontrib><creatorcontrib>Duca, Lorena</creatorcontrib><creatorcontrib>Campostrini, Natascia</creatorcontrib><creatorcontrib>Cortelezzi, Agostino</creatorcontrib><creatorcontrib>Corbella, Michela</creatorcontrib><creatorcontrib>Bosi, Alberto</creatorcontrib><creatorcontrib>Reda, Gianluigi</creatorcontrib><creatorcontrib>Olivieri, Oliviero</creatorcontrib><creatorcontrib>Cappellini, Maria Domenica</creatorcontrib><title>Hepcidin levels and their determinants in different types of myelodysplastic syndromes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Aged</subject><subject>Analysis</subject><subject>Anemia</subject><subject>Antimicrobial Cationic Peptides - blood</subject><subject>Biology</subject><subject>Blast cells</subject><subject>Blood cells</subject><subject>Blood Transfusion</subject><subject>C-reactive protein</subject><subject>Case-Control Studies</subject><subject>Chelating agents</subject><subject>Chelation</subject><subject>Chromatography</subject><subject>Chronic myelomonocytic leukemia</subject><subject>Disorders</subject><subject>Erythrocytes</subject><subject>Female</subject><subject>Ferritin</subject><subject>Ferritins - blood</subject><subject>Hematology</subject><subject>Hemodialysis</subject><subject>Hepcidin</subject><subject>Hepcidins</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Internal medicine</subject><subject>Iron</subject><subject>Iron - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21886780</pmid><doi>10.1371/journal.pone.0023109</doi><tpages>e23109</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-08, Vol.6 (8), p.e23109 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1308333818 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aged Analysis Anemia Antimicrobial Cationic Peptides - blood Biology Blast cells Blood cells Blood Transfusion C-reactive protein Case-Control Studies Chelating agents Chelation Chromatography Chronic myelomonocytic leukemia Disorders Erythrocytes Female Ferritin Ferritins - blood Hematology Hemodialysis Hepcidin Hepcidins Homeostasis Humans Inflammation Internal medicine Iron Iron - blood Leukemia Linear Models Male Medical prognosis Medicine Metabolism Models, Biological Modulators Mutation Myelodysplastic syndrome Myelodysplastic syndromes Myelodysplastic Syndromes - blood Myelodysplastic Syndromes - classification Myelomonocytic leukemia Patients Proteins Red blood cells Reference Values Refractory anemia Scientific imaging Sideroblasts Stem cells Transferrin Transferrins Transfusion Transplants & implants Variance analysis World Health Organization |
| title | Hepcidin levels and their determinants in different types of myelodysplastic syndromes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T21%3A06%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hepcidin%20levels%20and%20their%20determinants%20in%20different%20types%20of%20myelodysplastic%20syndromes&rft.jtitle=PloS%20one&rft.au=Santini,%20Valeria&rft.date=2011-08-19&rft.volume=6&rft.issue=8&rft.spage=e23109&rft.pages=e23109-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0023109&rft_dat=%3Cgale_plos_%3EA476881930%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1308333818&rft_id=info:pmid/21886780&rft_galeid=A476881930&rft_doaj_id=oai_doaj_org_article_c475cef064484c0cb2b4948e1ef12d73&rfr_iscdi=true |