Prognostic importance of Aurora Kinases and mitotic spindle genes transcript levels in Myelodysplastic syndrome. (January 2018)

• Record Type: Journal Article
• Authors: Borges, Daniela de Paula; dos Santos, Antônio Wesley Araújo; Paier, Carlos Roberto Koscky; Ribeiro, Howard Lopes; Costa, Marília Braga; Farias, Izabelle Rocha; de Oliveira, Roberta Taiane Germano; França, Ivo Gabriel da Frota; Cavalcante, Gabrielle Melo; Magalhães, Sílvia Maria Meira; Pinheiro, Ronald Feitosa
• Is Part Of: Leukemia research. Volume 64(2018)
• Page Start: 61
• Page End: 70
• Publication Date: 2018-01
• Subjects: Myelodysplastic syndrome -- Cell cycle -- Cancer biology -- Mitotic spindle -- Mitotic checkpoint; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2017.11.013
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: The presence of dysmegakaryopoiesis is associated with higher expression levels of CDC20 and TPX2. Overexpression of CDC20 mRNA is associated with a poor prognosis in MDS patients. Lower mRNA expression of AURKA and AURKB are associated with the presence of chromosomal alterations. MDS patients with higher p21 expression presented a low overall survival. 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 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/mm 3 . 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 8 g/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.