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DNA repair gene expressions are related to bone marrow cellularity in myelodysplastic syndrome
  1. Howard L Ribeiro Jr1,2,
  2. Allan Rodrigo S Maia1,2,
  3. Roberta Taiane G de Oliveira1,2,
  4. Marília Braga Costa1,2,
  5. Izabelle Rocha Farias1,2,
  6. Daniela de Paula Borges1,2,
  7. Juliana Cordeiro de Sousa1,2,
  8. Silvia Maria M Magalhães1,2,
  9. Ronald F Pinheiro1,2,3
  1. 1Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil
  2. 2Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil
  3. 3Post-Graduate Program of Pathology, Federal University of Ceara, Fortaleza, Ceara, Brazil
  1. Correspondence to Dr Ronald F Pinheiro, Federal University of Ceara, Center for Research and Drug Development (NPDM) R. Coronel Nunes de Melo, 1000–2° andar—Rodolfo Teófilo—CEP, Fortaleza, Ceara 60430–275, Brazil; ronaldfpinheiro{at}


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.


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  • Handling editor Mary Frances McMullin.

  • Contributors HLRJ, ARSM, RTGdO, MBC, IRF, DdPB, JCdS, SMMM and RFP designed the study. provided patient materials and were responsible for the collection and assembly of data. HLRJ, ARSM, RTGdO, MBC, IRF, DdPB, JCdS, SMMM and RFP performed the molecular procedures and analysed the data. All authors drafted and edited the manuscript and approved the final version of manuscript before publication.

  • Funding This study was conducted with partial support from the National Counsel of Technological and Scientific Development (CNPq) and Cearense Foundation for the Support of Scientific and Technological Development (FUNCAP).

  • Competing interests None declared.

  • Ethics approval The study was approved by the ethics committee of the Federal University of Ceara (No. 1.292.509) and conducted according to the Declaration of Helsinki.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.