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
Cancer Cytogenomic Laboratory, Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil; Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil.
Cancer Cytogenomic Laboratory, Federal University of Ceara, Fortaleza, Ceara, Brazil; Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil.
Leuk Res. 2018 Jan;64:61-70. doi: 10.1016/j.leukres.2017.11.013. Epub 2017 Nov 28.
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. 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.
骨髓增生异常综合征（MDS）是一组异质性克隆性疾病，其特征为骨髓功能不全、细胞凋亡增加以及急性白血病进展风险增加。与有丝分裂纺锤体相关的蛋白质（AURKA、AURKB、TPX2）、与有丝分裂检查点相关的蛋白质（MAD2、CDC20）以及细胞周期调节蛋白（p21）与染色体稳定性和肿瘤发展直接相关。本研究旨在采用实时PCR方法评估101例MDS患者中这些基因的mRNA表达水平。我们发现，巨核细胞生成异常的患者（p = 0.024）、血小板减少的患者（p = 0.000）以及高危患者（p = 0.014、0.018）中CDC20表达增加；2种或3种血细胞减少的患者（p = 0.000）以及中性粒细胞低于800/mm的患者中MAD2表达降低。TPX2在出现巨核细胞生成异常的患者中也过表达（p = 0.009）。在核型改变的患者（p = 0.000）、3个谱系出现发育异常的患者（p = 0.000；0.017）以及血红蛋白低于8g/dL的患者（p = 0.024）中观察到AURKA和AURKB表达降低。在低增生性MDS患者中，AURKA、AURKB和MAD2的表达降低（p = 0.000；0.001；0.025），这些患者染色体改变频率高且死亡率高。本研究再次证实极光激酶和有丝分裂纺锤体基因对MDS发病机制和临床演变的重要性。
