Increased expression of phosphorylated NBS1, a key molecule of the DNA damage response machinery, is an adverse prognostic factor in patients with de novo myelodysplastic syndromes

Maria Kefala, Sotirios G. Papageorgiou, Christos K. Kontos, Panagiota Economopoulou, Athanasios Tsanas, Vasiliki Pappa, Ioannis G. Panayiotides, Vassilios G. Gorgoulis, Eustratios Patsouris, Periklis G. Foukas

Research output: Contribution to journalArticlepeer-review

Abstract

The expression of activated forms of key proteins of the DNA damage response machinery (pNBS1, pATM and gamma H2AX) was assessed by means of immunohistochemistry in bone marrow biopsies of 74 patients with de novo myelodysplastic syndromes (MDS) and compared with 15 cases of de novo acute myeloid leukemia (AML) and 20 with reactive bone marrow histology. Expression levels were significantly increased in both MDS and AML, compared to controls, being higher in high-risk than in low-risk MDS. Increased pNBS1 and gamma H2AX expression possessed a significant negative prognostic impact for overall survival in MDS patients, whereas pNBS1 was an independent marker of poor prognosis. (C) 2013 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1576-1582
Number of pages7
JournalLeukemia Research
Volume37
Issue number11
Early online date5 Sep 2013
DOIs
Publication statusPublished - Nov 2013

Keywords

  • Myelodysplastic syndromes
  • DNA damage response
  • pNBS1
  • pATM
  • gamma H2AX
  • ACUTE MYELOID-LEUKEMIA
  • MYOGENIC DIFFERENTIATION
  • GENETIC INSTABILITY
  • BONE-MARROW
  • CELLS
  • COMPLEX
  • CANCER
  • ABNORMALITIES
  • ACTIVATION
  • ANEUPLOIDY

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