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.
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.
2nd Department of Pathology, University of Athens Medical School, "Attikon" University Hospital, Chaidari, Greece.
Maria
M
Kefala
Sotirios G
SG
Papageorgiou
Christos K
CK
Kontos
Panagiota
P
Economopoulou
Athanasios
A
Tsanas
Vasiliki
V
Pappa
Ioannis G
IG
Panayiotides
Vassilios G
VG
Gorgoulis
Eustratios
E
Patsouris
Periklis G
PG
Foukas
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D020732:Cytogenetic Analysis; D004249:DNA Damage; D005260:Female; D005500:Follow-Up Studies; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C468783:H2AX protein, human; D006657:Histones; C112156:NBN protein, human; D009687:Nuclear Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
DNA damage response; Myelodysplastic syndromes; pATM; pNBS1; γH2AX