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

doi:10.1016/j.leukres.2013.08.018

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

Leuk Res. 2013 Nov;37(11):1576-82. doi: 10.1016/j.leukres.2013.08.018. Epub 2013 Sep 5.

Authors

Maria Kefala¹, Sotirios G Papageorgiou, Christos K Kontos, Panagiota Economopoulou, Athanasios Tsanas, Vasiliki Pappa, Ioannis G Panayiotides, Vassilios G Gorgoulis, Eustratios Patsouris, Periklis G Foukas

Affiliation

¹ 2nd Department of Pathology, University of Athens Medical School, "Attikon" University Hospital, Chaidari, Greece.

PMID: 24054861
DOI: 10.1016/j.leukres.2013.08.018

Abstract

The expression of activated forms of key proteins of the DNA damage response machinery (pNBS1, pATM and γH2AX) 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 γH2AX expression possessed a significant negative prognostic impact for overall survival in MDS patients, whereas pNBS1 was an independent marker of poor prognosis.

Keywords: DNA damage response; Myelodysplastic syndromes; pATM; pNBS1; γH2AX.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Ataxia Telangiectasia Mutated Proteins / genetics
Ataxia Telangiectasia Mutated Proteins / metabolism*
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Cytogenetic Analysis
DNA Damage
Female
Follow-Up Studies
Histones / genetics
Histones / metabolism*
Humans
Immunoenzyme Techniques
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / metabolism
Leukemia, Myeloid, Acute / mortality*
Male
Middle Aged
Myelodysplastic Syndromes / genetics
Myelodysplastic Syndromes / metabolism
Myelodysplastic Syndromes / mortality*
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Phosphorylation
Prognosis
Survival Rate

Substances

Biomarkers, Tumor
Cell Cycle Proteins
H2AX protein, human
Histones
NBN protein, human
Nuclear Proteins
ATM protein, human
Ataxia Telangiectasia Mutated Proteins