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与纺锤体和检验点有丝分裂相关的蛋白强调了低增生性 MDS 的不同发病机制。

Proteins related to the spindle and checkpoint mitotic emphasize the different pathogenesis of hypoplastic MDS.

机构信息

Cancer Institute of Ceará/A.C. Camargo Hospital (Dinter-Minter), Fortaleza, Ceará, Brazil.

Federal University of Ceará, Brazil.

出版信息

Leuk Res. 2014 Feb;38(2):218-24. doi: 10.1016/j.leukres.2013.11.003. Epub 2013 Nov 13.

DOI:10.1016/j.leukres.2013.11.003
PMID:24314588
Abstract

Some studies show that alterations in expression of proteins related to mitotic spindle (AURORAS KINASE A and B) and mitotic checkpoint (CDC20 and MAD2L1) are involved in chromosomal instability and tumor progression in various solid and hematologic malignancies. This study aimed to evaluate these genes in MDS patients. The cytogenetics analysis was carried out by G-banding, AURKA and AURKB amplification was performed using FISH, and AURKA, AURKB, CDC20 and MAD2L1 gene expression was performed by qRT-PCR in 61 samples of bone marrow from MDS patients. AURKA gene amplification was observed in 10% of the cases, which also showed higher expression levels than the control group (p=0.038). Patients with normo/hypercellular BM presented significantly higher expression levels than hypocellular BM patients, but normo and hypercellular BM groups did not differ. After logistic regression analysis, our results showed that HIGH expression levels were associated with increased risk of developing normo/hypercellular MDS. It also indicated that age is associated with AURKA, CDC20 and MAD2L1 HIGH expression levels. The distinct expression of hypocellular patients emphasizes the prognostic importance of cellularity to MDS. The amplification/high expression of AURKA suggests that the increased expression of this gene may be related to the pathogenesis of disease.

摘要

一些研究表明,与有丝分裂纺锤体(AURORA 激酶 A 和 B)和有丝分裂检查点(CDC20 和 MAD2L1)相关的蛋白表达的改变与各种实体瘤和血液恶性肿瘤中的染色体不稳定性和肿瘤进展有关。本研究旨在评估 MDS 患者中的这些基因。通过 G 带分析进行细胞遗传学分析,使用 FISH 进行 AURKA 和 AURKB 扩增,通过 qRT-PCR 检测 61 例 MDS 患者骨髓样本中的 AURKA、AURKB、CDC20 和 MAD2L1 基因表达。在 10%的病例中观察到 AURKA 基因扩增,并且与对照组相比,其表达水平也更高(p=0.038)。BM 正常/高细胞患者的表达水平明显高于低细胞患者,但正常和高细胞组之间没有差异。经过逻辑回归分析,我们的结果表明,HIGH 表达水平与发生正常/高细胞 MDS 的风险增加相关。这也表明年龄与 AURKA、CDC20 和 MAD2L1 的 HIGH 表达水平相关。低细胞患者的不同表达强调了细胞计数对 MDS 的预后重要性。AURKA 的扩增/高表达表明该基因的表达增加可能与疾病的发病机制有关。

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