| OGG1 is a novel prognostic indicator in acute myeloid leukaemia. | |
| | |
MedLine Citation:
|
PMID: 20023702 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OGG1 (8-oxoguanine DNA glycosylase) constitutes a key component of the DNA base excision repair pathway, catalysing the removal of 8-oxoguanine nucleotides from DNA, thereby suppressing mutagenesis and cell death. We found that OGG1 expression was significantly downregulated by the RUNX1-ETO fusion protein product of the t(8;21) chromosome translocation in normal haematopoietic progenitor cells and in patients with acute myeloid leukaemia (AML). Further examination of OGG1 expression in 174 AML trial patients using Affymetrix microarrays showed that the prevalence rate of OGG1 expression was 33% and correlated strongly with adverse cytogenetics. OGG1-expressing patients had a worse relapse-free survival and overall survival and an increased risk of relapse at 5-years of follow-up. There remained a trend towards increased relapse rate among OGG1-expressing patients, even after adjusting for other known risk factors in comprehensive stratified analyses. We also determined a trend for OGG1 expression to have a more adverse impact on disease outcome in the context of the FLT3-ITD mutation. This study highlights OGG1 as a valuable prognostic marker that could be used to sub-stratify AML patients to predict those likely to fail conventional chemotherapies but those likely to benefit from novel therapeutic approaches that modulate DNA repair activity. |
| | |
Authors:
|
K Liddiard; R Hills; A K Burnett; R L Darley; A Tonks |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-21 |
Journal Detail:
|
Title: Oncogene Volume: 29 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2010 Apr |
Date Detail:
|
Created Date: 2010-04-01 Completed Date: 2010-04-23 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
|
Languages: eng Pagination: 2005-12 Citation Subset: IM |
Affiliation:
|
Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
DNA Glycosylases
/
genetics,
metabolism* Follow-Up Studies Guanine / analogs & derivatives*, metabolism Humans Leukemia, Myeloid, Acute / diagnosis*, enzymology, metabolism Mutation Prognosis* Tumor Markers, Biological / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
//Medical Research Council |
| Chemical | |
Reg. No./Substance:
|
0/Tumor Markers, Biological; 5614-64-2/8-hydroxyguanine; 73-40-5/Guanine; EC 3.2.2.-/DNA Glycosylases; EC 3.2.2.-/oxoguanine glycosylase 1, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Complex regulation of cell-cycle inhibitors by Fbxw7 in mouse embryonic fibroblasts.
Next Document: Self-association of adenovirus type 5 E1B-55 kDa as well as p53 is essential for their mutual intera...