title: Cell cycle and apoptosis regulatory gene expression in the bone marrow of patients with de novo myelodysplastic syndromes (MDS).
abstract: Deregulation of cell cycle and apoptosis pathways are known contributors to the pathogenesis of myelodysplastic syndromes (MDS). However, the underlying mechanisms are not fully clarified. The aim of our study was to examine mRNA expression levels of cell cycle and apoptosis regulatory genes, as well as the percentage of apoptotic and S phase cells and to correlate the findings with clinical characteristics and prognosis. Sixty patients with MDS, classified according to FAB (17 RA, five RARS, 19 RAEB, nine RAEBT, ten CMML) and WHO (ten RA, three RARS, seven RCMD, two RCMD-RS, 11 RAEBI, eight RAEBII, ten CMML, and nine AML) were included in the study. We found increased expression of anti-apoptotic bclxL and mcl1 genes and decreased expression of p21 gene in MDS patients. Moreover, we found increased expression of anti-apoptotic mcl1 gene in patients with higher than Intermediate-1 IPSS group. Multivariate analysis confirmed that combined expression of apoptotic caspases 8, 3, 6, 5, 2, 7, and Granzyme B was decreased in MDS patients. Regarding cell cycle regulatory genes expression, we demonstrated increased expression of cyclin D1 in patients with CMML Increased combined expression of cyclins B, C, D1, and D2 was found in patients with cytogenetic abnormalities. The two pathways seem to be interconnected as shown by the positive correlation between CDKs 1, 2, 4, p21 and the level of apoptosis and positive correlation between apoptotic caspase 3 expression and the percentage of S phase cells. In conclusion, our study showed altered expression of genes involved in apoptosis and cell cycle in MDS and increased expression of cyclin D1 in patients with CMML.
authors.affiliation: Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine, 1 Rimini Str., Haidari, Athens, Greece. chris_oiko@yahoo.com
authors.forename: Christina
authors.initials: C
authors.lastname: Economopoulou
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pappa
authors.forename: Sotiris
authors.initials: S
authors.lastname: Papageorgiou
authors.forename: Frieda
authors.initials: F
authors.lastname: Kontsioti
authors.forename: Panagiota
authors.initials: P
authors.lastname: Economopoulou
authors.forename: Efstratia
authors.initials: E
authors.lastname: Charitidou
authors.forename: Kostas
authors.initials: K
authors.lastname: Girkas
authors.forename: Violetta
authors.initials: V
authors.lastname: Kapsimali
authors.forename: Chrissoula
authors.initials: C
authors.lastname: Papasteriadi
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; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D016196:S Phase
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins