title: OGG1 is a novel prognostic indicator in acute myeloid leukaemia.
abstract: 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.affiliation: Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: K
authors.initials: K
authors.lastname: Liddiard
authors.forename: R
authors.initials: R
authors.lastname: Hills
authors.forename: A K
authors.initials: AK
authors.lastname: Burnett
authors.forename: R L
authors.initials: RL
authors.lastname: Darley
authors.forename: A
authors.initials: A
authors.lastname: Tonks
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000201:enzymology / Q000378:metabolism; D009154:Mutation; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human