{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:57:30Z","timestamp":1785585450896,"version":"3.56.0"},"reference-count":63,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100022030","name":"Silence Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and an increased risk of progression to acute myeloid leukemia (AML). Despite advances in supportive and targeted therapies, disease\u2010modifying interventions remain limited. Iron overload is increasingly recognized as a key driver of disease progression, amplifying oxidative stress and inflammation while impairing hematopoietic function. However, the mechanisms by which sustained iron excess contributes to disease evolution remain poorly understood. Hepcidin, the master regulator of systemic iron homeostasis, is produced by hepatocytes in response to iron and inflammatory cues and is negatively regulated by transmembrane protease serine 6 (TMPRSS6). Targeting TMPRSS6 to increase endogenous hepcidin offers a promising strategy to restrict iron overload and its inflammatory consequences. Here, we investigated hepatocyte\u2010targeted silencing of\n                    <jats:italic>Tmprss6<\/jats:italic>\n                    using a GalNAc\u2010conjugated siRNA (SLN124) in the NUP98\u2013HOXD13 (NHD13) mouse model of MDS. MDS and wild\u2010type mice received monthly subcutaneous SLN124 (3\u2009mg\/kg) or oral deferiprone (1.25\u2009mg\/mL). Iron burden in MDS mice strongly correlated with ASC\u2010speck formation in CD45\n                    <jats:sup>+<\/jats:sup>\n                    hematopoietic cells, consistent with inflammasome activation. Both SLN124 and deferiprone reduced tissue iron deposition and ASC\u2010speck abundance, with SLN124 producing the most pronounced effect. Long\u2010term SLN124 treatment delayed disease progression and significantly prolonged survival, with 30% of treated mice surviving beyond 450\u2009days compared with complete mortality by Day 420 in controls and deferiprone\u2010treated mice. These findings demonstrate that\n                    <jats:italic>Tmprss6<\/jats:italic>\n                    inhibition via SLN124 suppresses iron\u2010driven inflammation, and mitigated disease progression in MDS mice, establishing TMPRSS6 silencing as a promising disease\u2010modifying therapeutic approach.\n                  <\/jats:p>","DOI":"10.1002\/ajh.70391","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:58:15Z","timestamp":1780570695000},"page":"2105-2122","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Silencing of Tmprss6 Reduces Iron\u2010Induced Inflammation and Prolongs Survival in\n                    <scp>MDS<\/scp>\n                    Mice"],"prefix":"10.1002","volume":"101","author":[{"given":"Shahla","family":"Vilcassim","sequence":"first","affiliation":[{"name":"Centre of Cancer Research Hudson Institute of Medical Research  Melbourne Victoria Australia"},{"name":"School of Clinical Sciences at Monash Health Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuttanan","family":"Pholngam","sequence":"additional","affiliation":[{"name":"Centre of Cancer Research Hudson Institute of Medical Research  Melbourne Victoria Australia"},{"name":"Graduate Program in Molecular Medicine, Faculty of Science Mahidol University  Bangkok Thailand"},{"name":"Thalassemia Research Center Institute of Molecular Biosciences, Mahidol University  Nakhon Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rattanawan","family":"Thubthed","sequence":"additional","affiliation":[{"name":"Centre of Cancer Research Hudson Institute of Medical Research  Melbourne Victoria Australia"},{"name":"Department of Pathobiology, Faculty of Science Mahidol University  Bangkok Thailand"},{"name":"Faculty of Medicine Praboromarajchanok Institute, Ministry of Public Health  Nonthaburi Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiwaporn","family":"Nualkaew","sequence":"additional","affiliation":[{"name":"Centre of Cancer Research Hudson Institute of Medical Research  Melbourne Victoria Australia"},{"name":"Department of Medical Technology Walailak University  Nakhon Si Thammarat Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saovaros","family":"Svasti","sequence":"additional","affiliation":[{"name":"Thalassemia Research Center Institute of Molecular Biosciences, Mahidol University  Nakhon Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8962-7202","authenticated-orcid":false,"given":"Pornthip","family":"Chaichompoo","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Faculty of Science Mahidol University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kysenius","sequence":"additional","affiliation":[{"name":"Department of Anatomy &amp; Physiology and Centre for Muscle Research The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Crouch","sequence":"additional","affiliation":[{"name":"Department of Anatomy &amp; Physiology and Centre for Muscle Research The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle","family":"Dames","sequence":"additional","affiliation":[{"name":"Silence Therapeutics GmbH  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Eisermann","sequence":"additional","affiliation":[{"name":"Silence Therapeutics GmbH  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Martinez","sequence":"additional","affiliation":[{"name":"Silence Therapeutics PLC  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Schaeper","sequence":"additional","affiliation":[{"name":"Silence Therapeutics GmbH  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3072-3512","authenticated-orcid":false,"given":"Jim","family":"Vadolas","sequence":"additional","affiliation":[{"name":"Centre of Cancer Research Hudson Institute of Medical Research  Melbourne Victoria Australia"},{"name":"Department of Molecular and Translational Sciences Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Grigoriadis","sequence":"additional","affiliation":[{"name":"Centre of Cancer Research Hudson Institute of Medical Research  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-453068"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-017-2367-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000314"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.627662"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.232124"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.06.006"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.69"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16013"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-07-730556"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-023-01949-2"},{"issue":"2","key":"e_1_2_11_12_1","first-page":"283","article-title":"Pathogenesis and Inflammaging in Myelodysplastic Syndrome","volume":"110","author":"Villaume M. 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a GalNAc\u2010siRNA Conjugate Targeting TMPRSS6, Efficiently Prevents Iron Overload in Hereditary Haemochromatosis Type 1","volume":"3","author":"Altamura S.","year":"2019","journal-title":"Hema"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27015"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17428"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4794"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2025.107988"},{"key":"e_1_2_11_34_1","first-page":"880","article-title":"The Role of Redox\u2010Active Iron, Copper, Manganese, and Redox\u2010Inactive Zinc in Toxicity, Oxidative Stress, and Human Diseases","volume":"24","author":"Jomova K.","year":"2025","journal-title":"EXCLI 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