The prolyl-hydroxylase EGLN3 and not EGLN1 is inactivated by methylation in plasma cell neoplasia.
Eur J Haematol
; 84(1): 47-51, 2010 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-19737309
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), Waldenström'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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Paraproteinemias
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Procolágeno-Prolina Dioxigenasa
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Islas de CpG
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Metilación de ADN
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Silenciador del Gen
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Dioxigenasas
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Haematol
Asunto de la revista:
HEMATOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Grecia
Pais de publicación:
Reino Unido