The prolyl-hydroxylase EGLN3 and not EGLN1 is inactivated by methylation in plasma cell neoplasia

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dc.contributor.authorHatzimichael, E.en
dc.contributor.authorDasoula, A.en
dc.contributor.authorShah, R.en
dc.contributor.authorSyed, N.en
dc.contributor.authorPapoudou-Bai, A.en
dc.contributor.authorColey, H. M.en
dc.contributor.authorDranitsaris, G.en
dc.contributor.authorBourantas, K. L.en
dc.contributor.authorStebbing, J.en
dc.contributor.authorCrook, T.en
dc.date.accessioned2015-11-24T19:34:00Z
dc.date.available2015-11-24T19:34:00Z
dc.identifier.issn1600-0609-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/23587
dc.rightsDefault Licence-
dc.subjectAgeden
dc.subjectCell Line, Tumor/enzymologyen
dc.subjectCpG Islands/*geneticsen
dc.subject*DNA Methylationen
dc.subjectDNA, Neoplasm/geneticsen
dc.subjectDioxygenases/biosynthesis/*geneticsen
dc.subjectFemaleen
dc.subjectGene Expression Regulation, Enzymologicen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subject*Gene Silencingen
dc.subjectHumansen
dc.subjectLymphoma, B-Cell/classification/enzymology/geneticsen
dc.subjectMaleen
dc.subjectMiddle Ageden
dc.subjectMonoclonal Gammopathy of Undetermined Significance/enzymology/geneticsen
dc.subjectMultiple Myeloma/complications/enzymology/genetics/mortalityen
dc.subjectParaproteinemias/enzymology/*geneticsen
dc.subjectProcollagen-Proline Dioxygenase/biosynthesis/*geneticsen
dc.subjectWaldenstrom Macroglobulinemia/enzymology/geneticsen
dc.titleThe prolyl-hydroxylase EGLN3 and not EGLN1 is inactivated by methylation in plasma cell neoplasiaen
heal.abstractEGLN1 and EGLN3 are members of the egg-laying-defective 9 (EglN) prolyl-hydroxylases which during normoxia catalyse hydroxylation of the hypoxia-inducible factor (HIF)-1alpha, thereby promoting its ubiquitination by a complex containing the von Hippel-Lindau (VHL) tumour suppressor. EGLN3 also has pro-apoptotic activity in some cell types. Analyses of a well-characterised series of cases of plasma cell dyscrasias, including multiple myeloma (MM), Waldenstrom's macroglobulinaemia (WM) and monoclonal gammopathy of undetermined significance (MGUS) surprisingly demonstrated that the CpG island of EGLN3, and not EGLN1, is frequently methylated in these disorders. Multiple myeloma patients with a methylated EGLN3 promoter showed trends towards an increased risk of death, bone lytic lesions, anaemia, advanced stage of disease and the presence of extramedullary disease. Those individuals with methylation in the EGLN3 CpG island also had significantly lower albumin levels. These data suggest that the prolyl-hydroxylases may be a novel class of potential tumour suppressors in plasma cell neoplasia that warrant further investigation with regard to their potential utility as biomarkers. Moreover, we observed that EGLN3 is also methylated at high frequency in B-cell lymphoma subtypes, implying that loss of EGLN3 is an important epigenetic event not only in plasma cell neoplasias but also in B-cell neoplasias.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1111/j.1600-0609.2009.01344.x-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/19737309-
heal.identifier.secondaryhttp://onlinelibrary.wiley.com/store/10.1111/j.1600-0609.2009.01344.x/asset/j.1600-0609.2009.01344.x.pdf?v=1&t=h2boq8ws&s=0e72d00a6c72d669e1b18e41a9f70a1f034b400d-
heal.journalNameEur J Haematolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2010-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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