Τίτλος:
Expression analysis of proteins involved in the non homologous end joining DNA repair mechanism, in the bone marrow of adult de novo myelodysplastic syndromes
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Myelodysplastic syndromes (MDS) are characterized by genetic instability which is associated with abnormal DNA repair mechanisms. The most lethal type of DNA damage are double strand DNA breaks (DSBs), which are mainly repaired by Non Homologous End Joining Mechanism (NHEJ), whose core enzyme components include the Ku70/Ku80 heterodimer, DNA-PKcs, XRCC4 and DNA Ligase IV. The aim of the present study was the analysis of expression of proteins required for NHEJ in bone marrow cells of adult de novo MDS and their association with clinical characteristics and prognosis. Our analysis included 48 cases of MDS; 19 RA, 5 RARS, 19 RAEB, 3 RAEB-T, 1 CMML, 1 transformation to AML according to FAB classification. The expression of the enzymes Ku70, Ku80, XRCC4, DNA-PKcs and Ligase IV was determined by Western Blotting. The mean Ligase IV expression value was significantly lower in MDS patients compared to normal controls (0.53 vs. 0.78, p=0.03). A negative correlation was found between karyotype risk group and Ligase IV values. (p=0.05). Moreover, Ku70 expression levels were significantly lower in patients with a good prognosis karyotype (p=0.04). Furthermore, a negative correlation between Ku70 expression values and Hb levels was observed (p=0.04). Finally, a positive correlation was observed between enzyme Ku70 expression values and level of blasts (p=0.04). Our findings support a potential role of NHEJ enzyme Ligase IV in the pathogenesis of MDS. Larger numbers of cases need to be screened in order to draw definite conclusion © Springer-Verlag 2009.
Συγγραφείς:
Economopoulou, P.
Pappa, V.
Kontsioti, F.
Papageorgiou, S.
Foukas, P.
Liakata, E.
Economopoulou, C.
Vassilatou, D.
Ioannidou, E.-D.
Chondropoulos, S.
Tsirigotis, P.
Papageorgiou, E.
Dervenoulas, J.
Economopoulos, T.
Περιοδικό:
Annals of Hematology
Λέξεις-κλειδιά:
DNA; DNA dependent protein kinase; Ku antigen; ligase; ligase 4; nucleic acid binding protein; protein ku80; unclassified drug; XRCC4 protein; cell nucleus antigen; DNA binding protein; DNA dependent protein kinase; Ku antigen; nuclear protein; polydeoxyribonucleotide synthase; polydeoxyribonucleotide synthase (atp); PRKDC protein, human; protein; XRCC4 protein, human, acute granulocytic leukemia; adult; aged; article; bone marrow cell; chronic myelomonocytic leukemia; clinical article; controlled study; cytogenetics; DNA damage; DNA repair; female; human; human tissue; immunochemistry; karyotype; male; malignant transformation; myelodysplastic syndrome; pathogenesis; priority journal; prognosis; protein expression; protein isolation; refractory anemia; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; refractory anemia with ringed sideroblasts; Western blotting; bone marrow; case control study; double stranded DNA break; gene expression profiling; genetics; middle aged; pathology, Aged; Aged, 80 and over; Antigens, Nuclear; Bone Marrow; Case-Control Studies; DNA Breaks, Double-Stranded; DNA Ligases; DNA Repair; DNA-Activated Protein Kinase; DNA-Binding Proteins; Female; Gene Expression Profiling; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Nuclear Proteins; Prognosis; Proteins
DOI:
10.1007/s00277-009-0823-6
