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

磷酸化 NBS1 表达增加是 DNA 损伤反应机制的关键分子,也是新生骨髓增生异常综合征患者的不良预后因素

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作者: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

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.

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