The prolyl-hydroxylase EGLN3 and not EGLN1 is inactivated by methylation in plasma cell neoplasia
Φόρτωση...
Ημερομηνία
Συγγραφείς
Hatzimichael, E.
Dasoula, A.
Shah, R.
Syed, N.
Papoudou-Bai, A.
Coley, H. M.
Dranitsaris, G.
Bourantas, K. L.
Stebbing, J.
Crook, T.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Eur J Haematol
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
EGLN1 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.
Περιγραφή
Λέξεις-κλειδιά
Aged, Cell Line, Tumor/enzymology, CpG Islands/*genetics, *DNA Methylation, DNA, Neoplasm/genetics, Dioxygenases/biosynthesis/*genetics, Female, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, *Gene Silencing, Humans, Lymphoma, B-Cell/classification/enzymology/genetics, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance/enzymology/genetics, Multiple Myeloma/complications/enzymology/genetics/mortality, Paraproteinemias/enzymology/*genetics, Procollagen-Proline Dioxygenase/biosynthesis/*genetics, Waldenstrom Macroglobulinemia/enzymology/genetics
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/19737309
http://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
http://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
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής