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Iron homeostasis governs erythroid phenotype in polycythemia vera.
Bennett, Cavan; Jackson, Victoria E; Pettikiriarachchi, Anne; Hayman, Thomas; Schaeper, Ute; Moir-Meyer, Gemma; Fielding, Katherine; Ataide, Ricardo; Clucas, Danielle; Baldi, Andrew; Garnham, Alexandra L; Li-Wai-Suen, Connie S N; Loughran, Stephen J; Baxter, E Joanna; Green, Anthony R; Alexander, Warren S; Bahlo, Melanie; Burbury, Kate; Ng, Ashley P; Pasricha, Sant-Rayn.
Afiliación
  • Bennett C; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Jackson VE; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
  • Pettikiriarachchi A; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Hayman T; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
  • Schaeper U; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Moir-Meyer G; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Fielding K; Silence Therapeutics GmbH, Berlin, Germany.
  • Ataide R; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Clucas D; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
  • Baldi A; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Garnham AL; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
  • Li-Wai-Suen CSN; Diagnostic Haematology, The Royal Melbourne Hospital, Parkville, VIC, Australia.
  • Loughran SJ; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Baxter EJ; Department of Infectious Diseases, Peter Doherty Institute, University of Melbourne, Parkville, VIC, Australia.
  • Green AR; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Alexander WS; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
  • Bahlo M; Diagnostic Haematology, The Royal Melbourne Hospital, Parkville, VIC, Australia.
  • Burbury K; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Ng AP; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
  • Pasricha SR; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
Blood ; 141(26): 3199-3214, 2023 06 29.
Article en En | MEDLINE | ID: mdl-36928379
Polycythemia vera (PV) is a myeloproliferative neoplasm driven by activating mutations in JAK2 that result in unrestrained erythrocyte production, increasing patients' hematocrit and hemoglobin concentrations, placing them at risk of life-threatening thrombotic events. Our genome-wide association study of 440 PV cases and 403 351 controls using UK Biobank data showed that single nucleotide polymorphisms in HFE known to cause hemochromatosis are highly associated with PV diagnosis, linking iron regulation to PV. Analysis of the FinnGen dataset independently confirmed overrepresentation of homozygous HFE variants in patients with PV. HFE influences the expression of hepcidin, the master regulator of systemic iron homeostasis. Through genetic dissection of mouse models of PV, we show that the PV erythroid phenotype is directly linked to hepcidin expression: endogenous hepcidin upregulation alleviates erythroid disease whereas hepcidin ablation worsens it. Furthermore, we demonstrate that in PV, hepcidin is not regulated by expanded erythropoiesis but is likely governed by inflammatory cytokines signaling via GP130-coupled receptors. These findings have important implications for understanding the pathophysiology of PV and offer new therapeutic strategies for this disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Policitemia Vera Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Blood Año: 2023 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Policitemia Vera Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Blood Año: 2023 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos