Prognostic importance of Aurora Kinases and mitotic spindle genes transcript levels in Myelodysplastic syndrome

Myelodysplastic syndrome (MDS) are a heterogeneous group of clonal disease characterized by insufficiency of bone marrow, increase of apoptosis and increased risk of acute leukemia progression. Proteins related to the mitotic spindle (AURKA, AURKB, TPX2), to the mitotic checkpoint (MAD2, CDC20) and the regulation of the cell cycle (p21) are directly related to chromosomal stability and tumor development. This study aimed to evaluate the mRNA expression levels of these genes in 101 MDS patients using a real-time PCR methodology. We identified that CDC20 expression are increased in patients with dysmegakaryopoiesis (p=0.024), thrombocytopenia (p=0.000) and high-risk patients (p=0.014, 0.018) MAD2 expression 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 expression were observed in patients with altered karyotype (p=0.000), who presented dysplasia in 3 lineages (p=0.000; 0.017) and hemoglobin inferior to 8g/dL (p=0.024). The expression of AURKA, AURKB and MAD2 (p=0.000; 0.001; 0.025) were decreased in patients with hypoplastic MDS, associated with high frequency of chromosomal alterations and high mortality rate. This study reaffirms the importance of aurora kinases and mitotic spindle genes to the pathogenesis and clinical evolution of MDS.