title: Expression analysis of proteins involved in the non homologous end joining DNA repair mechanism, in the bone marrow of adult de novo myelodysplastic syndromes.
abstract: 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 suppor-t 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.
authors.affiliation: Second Department of Internal Medicine, Propaedeutic, University of Athens, Medical School, University General Hospital Attikon, 12 462 Haidari, Greece. panagiota_oiko@hotmail.com
authors.forename: Panagiota
authors.initials: P
authors.lastname: Economopoulou
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pappa
authors.forename: Frieda
authors.initials: F
authors.lastname: Kontsioti
authors.forename: Sotirios
authors.initials: S
authors.lastname: Papageorgiou
authors.forename: Periklis
authors.initials: P
authors.lastname: Foukas
authors.forename: Elisavet
authors.initials: E
authors.lastname: Liakata
authors.forename: Christina
authors.initials: C
authors.lastname: Economopoulou
authors.forename: Diamantina
authors.initials: D
authors.lastname: Vassilatou
authors.forename: Eleni-Dikala
authors.initials: ED
authors.lastname: Ioannidou
authors.forename: Spiridon
authors.initials: S
authors.lastname: Chondropoulos
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsirigotis
authors.forename: Efstathios
authors.initials: E
authors.lastname: Papageorgiou
authors.forename: John
authors.initials: J
authors.lastname: Dervenoulas
authors.forename: Theofanis
authors.initials: T
authors.lastname: Economopoulos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear / Q000235:genetics; D001853:Bone Marrow; D016022:Case-Control Studies; D053903:DNA Breaks, Double-Stranded; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D051747:DNA-Activated Protein Kinase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D011506:Proteins / Q000235:genetics*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C000607893:LIG4 protein, human; D009687:Nuclear Proteins; D011506:Proteins; C101467:XRCC4 protein, human; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D011088:DNA Ligases; D000072481:DNA Ligase ATP