Estudo de alvos moleculares relacionados à mitose e ao ciclo celular em pacientes portadores de síndrome mielodisplásica

Abstract

Myelodysplastic syndrome (MDS) are a heterogeneous group of clonal disease characterized by insufficiency of bone marrow, increase of apoptosis and increased risk of acute myeloid leukemia (AML) progression. Proteins related to the mitotic spindle (AURKA, AURKB, TPX2), to the mitotic checkpoint (MAD2, CDC20) and the regulation of the cell cycle (CDKN1A) are directly related to chromosome stability and tumor development. This study aimed to evaluate the mRNA expression levels of these genes in 101 MDS patients and 10 healthy volunteers, using a real-time PCR methodology. After the analysis of mRNA expression, we identified that CDC20 gene expression levels are increased in patients with dysmegakaryopoiesis (p=0.024), thrombocytopenia (p=0.000) and high-risk patients (p=0.014, 0.018.) MAD2 expression levels are decreased in patients with 2 or 3 cytopenias (p=0.000) and neutrophil below 800/mm3. TPX2 is also overexpressed in patients presenting dysmegakaryopoiesis (p=0.009). A decrease in AURKA and AURKB gene expression levels were observed in patients with altered karyotype (p=0.000), who presented dysplasia in 3 lineages (p=0.000; 0.017) (AURKA) and hemoglobin inferior to 8g/dL (p=0.024) (AURKB). Patients with decreased AURKA and AURKB showed low overall survival and increased levels of CDKN1A expression are associated with poorer overall survival (p=0.000). The mRNA expression of AURKA, AURKB and MAD2 (p=0.000; p=0.001; p=0.025) were decreased in patients with hypoplastic MDS, associated with a high frequency of chromosomal alterations and high mortality rate. In this investigation, we found significant clinical correlations regarding AURKA, AURKB, MAD2, CDC20, TPX2 e CDKN1A, reaffirming the importance of studying these genes in MDS patients, to provide a better comprehension of the syndrome pathogenesis and evolution.