Expression analysis of proteins involved in the non homologous end joining DNA repair mechanism, in the bone marrow of adult de novo myelodysplastic syndromes.
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.
Economopoulou
Panagiota
P
Second Department of Internal Medicine, Propaedeutic, University of Athens, Medical School, University General Hospital Attikon, 12 462 Haidari, Greece. panagiota_oiko@hotmail.com
Pappa
Vassiliki
V
Kontsioti
Frieda
F
Papageorgiou
Sotirios
S
Foukas
Periklis
P
Liakata
Elisavet
E
Economopoulou
Christina
C
Vassilatou
Diamantina
D
Ioannidou
Eleni-Dikala
ED
Chondropoulos
Spiridon
S
Tsirigotis
Panagiotis
P
Papageorgiou
Efstathios
E
Dervenoulas
John
J
Economopoulos
Theofanis
T
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*
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