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Objective: To evaluate the expression of genes related to nuclear excision ( ERCC8 , XPA and XPC ), homologous recombination and non-homologous end-joining ( ATM , BRCA1 , BRCA2 and LIG4 ) repair mechanisms, using quantitative PCR methodologies, and it relation with bone marrow cellularity in myelodysplastic syndrome (MDS)., Methods and Results: A total of 51 adult de novo patients with MDS (3 refractory anaemia (RA), 11 refractory anaemia with ringed sideroblasts (RARS), 28 refractory cytopenia with multilineage dysplasia (RCMD), 3 refractory anaemia with excess blasts type I (RAEB-I), 5 refractory anaemia with excess blasts type II (RAEB-II), and 1 chronic myelomonocytic leukaemia (CMML) were evaluated. For karyotype, 16.2% patients were defined as very low prognosis, 59.5% low risk, 8.1% intermediate risk, 5.4% high risk and 10.8% very high risk. For bone marrow cellularity, 17.6%, 17.6% and 64.7% presented as hypocellular, normocellular and hypercellular, respectively. Patients with hypocellular MDS had significantly decreased expression of ATM (p=0.000) , BRCA1 (p=0.014), BRCA2 (p=0.003) , LIG4 (p=0.004) and ERCC8 (p=0.000) than those with normocellular/hypercellular bone marrow, whereas XPA (p=0.049) and XPC (p=0.000) genes were increased. In patients with hypoplastic MDS, a low expression of ATM (p=0.0268), LIG4 (p=0.0199) and ERCC8 (p=0.0493) was significantly associated with the presence of chromosomal abnormalities. We detected positive correlations between BRCA1 and BRCA2 (r=0.416; p=0.007), ATM and LIG4 (r=0.472; p=0.001), LIG4 and BRCA1 (r=0.333; p=0.026), LIG4 and BRCA2 (r=0.334; p=0.025), ATM and XPA (r=0.377; p=0.008), ATM and XPC (r=0.287; p=0.046), LIG4 and XPC (r=0.371; p=0.007) and XPA and XPC genes (r=0.895; p=0.0000). We also found among all patients evaluated that correlation with LIG4 occurred most often., Conclusions: These correlations demonstrate the important intrinsic relations between single and double DNA strand breaks genes in MDS, emphasising that these genes are related to MDS pathogenesis., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Some studies show that alterations in DNA repair genes polymorphisms are associated with the pathogenesis and susceptibility of Myelodysplastic Syndrome (MDS). We genotyped 60 MDS patients for six DNA repair gene polymorphisms: BRCA1 rs4793191, BRCA2 rs9567623, RAD51 rs1801320, XRCC5 rs3835, XRCC6 rs2267437 and LIG4 rs1805388. The G/C heterozygote genotype of rs1801320 polymorphism was associated with a decreased chance of developing MDS (p = 0.05). Additionally, the G/G homozygous genotype was associated with the presence of one cytopenia in whole blood. The genotype C/G and CG + GG of the rs2267437 polymorphism was associated with normal karyotype (p = 0.010) and bone marrow cellularity normocellular + hypercellular (p = 0.023). We found that the A/G heterozygous genotype of the rs3835 polymorphism is associated with decreased chance of developing MDS (p < 0.001). These results support the importance of RAD51, XRCC5 and XRCC6 genes polymorphisms in the maintenance of genomic stability promoting a better understanding of the genesis and etiology of MDS., (Copyright © 2014 John Wiley & Sons, Ltd.)

Objective: A relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated., Design, Setting and Participants: An observational cross-sectional study involving 87 healthy individuals and 78 patients with myelodysplastic syndromes (MDS) with and without IOL, seen at University Hospital of the Federal University of Ceará, Brazil, between May 2010 and September 2011., Methods: IOL was defined using repeated measures of serum ferritin ≥1000 ng/mL. Variations in the HFE gene were investigated using PCR/restriction fragment length polymorphism (RFLP). The biomarkers of oxidative stress (plasmatic malonaldehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were determined by spectrophotometry., Results: The HFE gene variations were identified in 24 patients (30.77%) and 5 volunteers (5.74%). The H63D variant was observed in 35% and the C282Y variant as heterozygous in 5% of patients with MDS with IOL. One patient showed double heterozygous variant (C282Y/H63D) and serum ferritin of 11,649 ng/mL. In patients without IOL, the H63D variant was detected in 29.34%. Serum MDA levels were highest in patients with MDS with IOL, with a significant difference when compared with patients without IOL and healthy volunteers, pointing to the relationship between IOL and oxidative stress. The GPx and SOD were also significantly higher in these patients, indicating that lipid peroxidation increase was followed by an increase in antioxidant capacity. Higher ferritin levels were observed in patients with HFE gene variation. 95.7% of patients with MDS with the presence of HFE gene variations had received more of 20 transfusions., Conclusions: We observed a significant increase in MDA levels in patients with MDS and IOL, suggesting an increased lipid peroxidation in these patients. The accumulation of MDA alters the organisation of membrane phospholipids, contributing to the process of cellular degeneration. Results show that excess iron intensifies the process of cell damage through oxidative stress., Trial Registration Number: Local Ethics Committee (licence 150/2009)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)