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.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Ataxia Telangiectasia Mutated Proteins / genetics
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Ataxia Telangiectasia Mutated Proteins / metabolism*
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cytogenetic Analysis
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DNA Damage
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Female
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Follow-Up Studies
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Histones / genetics
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Histones / metabolism*
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Humans
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Immunoenzyme Techniques
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Leukemia, Myeloid, Acute / genetics
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Leukemia, Myeloid, Acute / metabolism
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Leukemia, Myeloid, Acute / mortality*
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Male
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Middle Aged
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Myelodysplastic Syndromes / genetics
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Myelodysplastic Syndromes / metabolism
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Myelodysplastic Syndromes / mortality*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphorylation
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Prognosis
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Survival Rate
Substances
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Biomarkers, Tumor
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Cell Cycle Proteins
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H2AX protein, human
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Histones
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NBN protein, human
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Nuclear Proteins
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins