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dc.contributor.authorZahoor, Muhammad
dc.contributor.authorWesthrin, Marita
dc.contributor.authorAass, Kristin Roseth
dc.contributor.authorMoen, Siv Helen
dc.contributor.authorMisund, Kristine
dc.contributor.authorPsonka-Antonczyk, Katarzyna Maria
dc.contributor.authorGiliberto, Mariaserena
dc.contributor.authorBuene, Glenn
dc.contributor.authorSundan, Anders
dc.contributor.authorWaage, Anders
dc.contributor.authorSponaas, Anne-Marit
dc.contributor.authorStandal, Therese
dc.date.accessioned2018-04-23T12:55:14Z
dc.date.available2018-04-23T12:55:14Z
dc.date.created2018-01-12T11:23:49Z
dc.date.issued2017
dc.identifier.citationBlood Advances. 2017, 27 (1), 2656-2666.nb_NO
dc.identifier.issn2473-9537
dc.identifier.urihttp://hdl.handle.net/11250/2495503
dc.description.abstractMultiple myeloma (MM) is a hematologic cancer characterized by expansion of malignant plasma cells in the bone marrow. Most patients develop an osteolytic bone disease, largely caused by increased osteoclastogenesis. The myeloma bone marrow is hypoxic, and hypoxia may contribute to MM disease progression, including bone loss. Here we identified interleukin-32 (IL-32) as a novel inflammatory cytokine expressed by a subset of primary MM cells and MM cell lines. We found that high IL-32 gene expression in plasma cells correlated with inferior survival in MM and that IL-32 gene expression was higher in patients with bone disease compared with those without. IL-32 was secreted from MM cells in extracellular vesicles (EVs), and those EVs, as well as recombinant human IL-32, promoted osteoclast differentiation both in vitro and in vivo. The osteoclast-promoting activity of the EVs was IL-32 dependent. Hypoxia increased plasma-cell IL-32 messenger RNA and protein levels in a hypoxia-inducible factor 1α–dependent manner, and high expression of IL-32 was associated with a hypoxic signature in patient samples, suggesting that hypoxia may promote expression of IL-32 in MM cells. Taken together, our results indicate that targeting IL-32 might be beneficial in the treatment of MM bone disease in a subset of patients.nb_NO
dc.language.isoengnb_NO
dc.publisherAmerican Society of Hematologynb_NO
dc.relation.urihttp://www.bloodadvances.org/content/1/27/2656?sso-checked=true
dc.titleHypoxia promotes IL-32 expression in myeloma cells, and high expression is associated with poor survival and bone lossnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.pagenumber2656-2666nb_NO
dc.source.volume27nb_NO
dc.source.journalBlood Advancesnb_NO
dc.source.issue1nb_NO
dc.identifier.doi10.1182/bloodadvances.2017010801
dc.identifier.cristin1541515
dc.relation.projectNorges forskningsråd: 193072nb_NO
dc.relation.projectKreftforeningen: 4500930nb_NO
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.relation.projectSamarbeidsorganet mellom Helse Midt-Norge og NTNU: 90171600nb_NO
dc.relation.projectSamarbeidsorganet mellom Helse Midt-Norge og NTNU: 90061000nb_NO
dc.description.localcode© 2017 by The American Society of Hematologynb_NO
cristin.unitcode194,65,15,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.ispublishedtrue
cristin.fulltextoriginal


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