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dc.contributor.authorHatzimichael, E
dc.contributor.authorDasoula, A
dc.contributor.authorShah, R
dc.contributor.authorSyed, N
dc.contributor.authorPapoudou-Bai, A
dc.contributor.authorColey, HM
dc.contributor.authorDranitsaris, G
dc.contributor.authorBourantas, KL
dc.contributor.authorStebbing, J
dc.contributor.authorCrook, T
dc.identifier.citationEUROPEAN JOURNAL OF HAEMATOLOGY, 2010, 84 pp. 47 - 51
dc.description.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)-1 alpha, 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.
dc.format.extent47 - 51
dc.titleThe prolyl-hydroxylase EGLN3 and not EGLN1 is inactivated by methylation in plasma cell neoplasia
dc.typeJournal Article
rioxxterms.typeJournal Article/Review
pubs.notesaffiliation: Hatzimichael, E (Reprint Author), Univ Ioannina, Dept Haematol, Med Sch Ioannina, GR-45110 Ioannina, Greece. Hatzimichael, Eleftheria; Dasoula, Aggeliki; Bourantas, Konstantinos L., Univ Ioannina, Dept Haematol, Med Sch Ioannina, GR-45110 Ioannina, Greece. Shah, Reshma; Syed, Nelofer, Inst Canc Res, Lab Canc Genet & Epigenet, London SW3 6JB, England. Papoudou-Bai, Alexandra, Univ Ioannina, Dept Pathol, Med Sch Ioannina, GR-45110 Ioannina, Greece. Coley, Helen M., Univ Surrey, Postgrad Med Sch, Guildford GU2 5XH, Surrey, England. Dranitsaris, George, Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. Stebbing, Justin; Crook, Tim, Univ London Imperial Coll Sci Technol & Med, Dept Med Oncol, Charing Cross Hosp, London, England. keywords: multiple myeloma; plasma cell neoplasia; methylation; EGLN1; EGLN3; prolyl-hydroxylase keywords-plus: MULTIPLE-MYELOMA; TUMOR-SUPPRESSOR; CANCER; HYPOXIA; DISEASE; GROWTH; FAMILY; GENE; HIF research-areas: Hematology web-of-science-categories: Hematology author-email: [email protected] orcid-numbers: Hatzimichael, Eleftheria/0000-0002-4408-5646 funding-acknowledgement: Research Committee of the University of Ioannina [22130]; Janssen-Cilag; Pharmaceutical; S.A.C.I., Roche (Hellas) S.A; Genesis Pharma S.A. funding-text: The study was partly supported by the Research Committee of the University of Ioannina (Programme #22130) from grants by Janssen-Cilag, Pharmaceutical, S.A.C.I., Roche (Hellas) S.A and Genesis Pharma S.A. number-of-cited-references: 14 times-cited: 25 usage-count-last-180-days: 0 usage-count-since-2013: 2 journal-iso: Eur. J. Haematol. doc-delivery-number: 531GZ unique-id: ISI:000272653800005 da: 2018-08-23
pubs.notesNot known
pubs.embargo.termsNot known
dc.contributor.icrauthorSyed, Neloferen

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