Differential expression of homologous recombination DNA repair genes in the early and advanced stages of myelodysplastic syndrome
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
PubMed
28681469
DOI
10.1111/ejh.12920
Knihovny.cz E-resources
- Keywords
- RAD51, DNA repair, homologous recombination, myelodysplastic syndrome,
- MeSH
- Biomarkers MeSH
- Chromosome Aberrations MeSH
- DNA-Binding Proteins genetics metabolism MeSH
- Adult MeSH
- Bone Marrow pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Myelodysplastic Syndromes genetics metabolism mortality pathology MeSH
- DNA Repair MeSH
- Prognosis MeSH
- Gene Expression Regulation * MeSH
- Recombinational DNA Repair genetics MeSH
- Rad51 Recombinase genetics metabolism MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Biomarkers MeSH
- DNA-Binding Proteins MeSH
- Rad51 Recombinase MeSH
- RPA3 protein, human MeSH Browser
- XRCC2 protein, human MeSH Browser
BACKGROUND: The high incidence of mutations and cytogenetic abnormalities in patients with myelodysplastic syndrome (MDS) suggests that defects in DNA repair mechanisms. We monitored DNA repair pathways in MDS and their alterations during disease progression. METHODS: Expression profiling of DNA repair genes was performed on CD34+ cells, and paired samples were used for monitoring of RAD51 and XRCC2 gene expression during disease progression. Immunohistochemical staining for RAD51 was done on histology samples. RESULTS: RAD51 and XRCC2 showed differential expression between low-risk and high-risk MDS (P<.0001), whereas RPA3 was generally decreased among the entire cohort (FC=-2.65, P<.0001). We demonstrated that RAD51 and XRCC2 expression gradually decreased during the progression of MDS. Down-regulation of XRCC2 and RAD51 expression was connected with abnormalities on chromosome 7 (P=.0858, P=.0457). Immunohistochemical staining revealed the presence of RAD51 only in the cytoplasm in low-risk MDS, while in both the cytoplasm and nucleus in high-risk MDS. The multivariate analysis identified RAD51 expression level (HR 0.49; P=.01) as significant prognostic factor for overall survival of patients with MDS. CONCLUSIONS: Our study demonstrates that the expression of DNA repair factors, primarily RAD51 and XRCC2, is deregulated in patients with MDS and presents a specific pattern with respect to prognostic categories.
1st Internal Clinic Clinic of Hematology General University Hospital Prague Czech Republic
Institute of Hematology and Blood Transfusion Prague Czech Republic
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