Análise dos genes CDC20 e CEP55 na patogênese da síndrome mielodisplásica e suas alterações cromossômicas

Abstract

Myelodysplastic syndrome (MDS) is characterized by a heterogeneous group of clonal diseases of hematopoietic progenitor cells that present a series of distinct biological characteristics. The presence of a cytogenetic change in MDS is important for diagnosis, prognosis and therapeutic guidance. Genes involved in the process of transition from metaphase to anaphase and DNA repair may be involved in the genesis of chromosomal changes in patients with Myelodysplastic Syndrome. The aim of this study is to analyze the CDC20 and CEP55 genes in patients diagnosed with MDS, associating the findings with cytogenetic changes, clinical and laboratory variables of prognostic impact. The expression of 45 patients with MDS and 5 controls was analyzed using real-time PCR (RT-qPCR) methodology. For the cytogenetic study, a bone marrow karyotype examinant with short-term culture was performed by G-band. MDS patients showed increased expression of the CDC20 and CEP55 genes compared to healthy individuals (p = 0.000 and p = 0.000). Hyperexpression of CDC20 and CEP55 was observed in patients with abnormal karyotype and aneuploid karyotype when compared with patients with normal karyotype (p = 0.000 and p = 0.001; p = 0.013 and p = 0.022, respectively). Additionally, in patients with karyotype with deletion (7q) and complex karyotype (p = 0.005; p = 0.019) there was overexpression of CEP55, while patients with non-complex karyotype (p=0.002) and with deletion (5q) and without del (5q) (p = 0.000; p = 0.005) showed overexpressed CDC20 when compared to patients with normal karyotype. Regarding the findings of bone marrow and peripheral blood, the expression of CEP55 and CDC20 was significantly higher (p = 0.040 and p = 0.005) in patients with dysmegakaryopoiesis. There is increased expression of the CDC20 gene in patients with hemoglobin <10 g / dL (p = 0.033), ring sideroblasts >15% (p = 0.034), as well as patients who are part of the ARSA subgroup (p = 0.025) (WHO, 2008). Patients older than 60 years showed increased expression of CEP55 (p = 0.026). In Pearson's correlation analysis, the CDC20 and CEP55 genes showed moderate positive correlation (r = 0.646) with an influence of 43% of the expression of one on the other, suggesting that these genes work together. In a correlation analysis of CEP55 with genes in the single strand DNA repair pathway (database of the Cancer Cytogenomics Laboratory), high positive correlations were detected with the XPA, XPG and CSB genes (r = 0.674; r = 0.606 and r = 0.647, respectively). Regarding the CDC20 gene and mitotic spindle verification genes, high positive correlations were detected with the TPX2, AURB and MAD2 genes (r = 0.560; r = 0.652 and r = 0.576). The increased expression of CDC20 and CEP55 are particularly associated with chromosomal changes in MDS.