Differential expression of homologous recombination DNA repair genes in the early and advanced stages of myelodysplastic syndrome
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28681469
DOI
10.1111/ejh.12920
Knihovny.cz E-zdroje
- Klíčová slova
- RAD51, DNA repair, homologous recombination, myelodysplastic syndrome,
- MeSH
- biologické markery MeSH
- chromozomální aberace MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- dospělí MeSH
- kostní dřeň patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- myelodysplastické syndromy genetika metabolismus mortalita patologie MeSH
- oprava DNA MeSH
- prognóza MeSH
- regulace genové exprese * MeSH
- rekombinační oprava DNA genetika MeSH
- rekombinasa Rad51 genetika metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- DNA vazebné proteiny MeSH
- rekombinasa Rad51 MeSH
- RPA3 protein, human MeSH Prohlížeč
- XRCC2 protein, human MeSH Prohlížeč
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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