DNA repair gene expressions are related to bone marrow cellularity in myelodysplastic syndrome.

Objective: To evaluate the expression of genes related to nuclear excision (, and ), homologous recombination and non-homologous end-joining (, , and ) 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 (p=0.000) (p=0.014), (p=0.003) (p=0.004) and (p=0.000) than those with normocellular/hypercellular bone marrow, whereas (p=0.049) and (p=0.000) genes were increased. In patients with hypoplastic MDS, a low expression of (p=0.0268), (p=0.0199) and (p=0.0493) was significantly associated with the presence of chromosomal abnormalities. We detected positive correlations between and (r=0.416; p=0.007), and (r=0.472; p=0.001), and (r=0.333; p=0.026), and (r=0.334; p=0.025), and (r=0.377; p=0.008), and (r=0.287; p=0.046), and (r=0.371; p=0.007) and and genes (r=0.895; p=0.0000). We also found among all patients evaluated that correlation with 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.