Differential expression of homologous recombination DNA repair genes in the early and advanced stages of myelodysplastic syndrome

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10364611" target="_blank" >RIV/00216208:11110/17:10364611 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/17:10364611 RIV/00064203:_____/17:10364611 RIV/00023736:_____/17:00011769 RIV/00064165:_____/17:10364611

Výsledek na webu

<a href="http://dx.doi.org/10.1111/ejh.12920" target="_blank" >http://dx.doi.org/10.1111/ejh.12920</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/ejh.12920" target="_blank" >10.1111/ejh.12920</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Differential expression of homologous recombination DNA repair genes in the early and advanced stages of myelodysplastic syndrome

Popis výsledku v původním jazyce

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&lt;.0001), whereas RPA3 was generally decreased among the entire cohort (FC=-2.65, P&lt;.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.

Název v anglickém jazyce

Differential expression of homologous recombination DNA repair genes in the early and advanced stages of myelodysplastic syndrome

Popis výsledku anglicky

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&lt;.0001), whereas RPA3 was generally decreased among the entire cohort (FC=-2.65, P&lt;.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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Haematology

ISSN

0902-4441

e-ISSN

—

Svazek periodika

99

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

DK - Dánské království

Počet stran výsledku

9

Strana od-do

323-331

Kód UT WoS článku

000411525900005

EID výsledku v databázi Scopus

2-s2.0-85029796452