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有丝分裂检查点和纺锤体的蛋白质与骨髓增生异常综合征患者的染色体不稳定及不良预后相关。

Proteins of the mitotic checkpoint and spindle are related to chromosomal instability and unfavourable prognosis in patients with myelodysplastic syndrome.

作者信息

Genga Kelly Roveran, Filho Francisco Dário Rocha, Ferreira Francisco Valdeci de Almeida, de Sousa Juliana Cordeiro, Studart Fernando Sergio, Magalhães Silvia Maria Meira, Heredia Fabíola Fernandes, Pinheiro Ronald Feitosa

机构信息

Department of Pathology, Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Ceará, Brazil.

Department of Pathology, Federal University of Ceará, Fortaleza, Ceará, Brazil.

出版信息

J Clin Pathol. 2015 May;68(5):381-7. doi: 10.1136/jclinpath-2014-202728. Epub 2015 Jan 30.

DOI:10.1136/jclinpath-2014-202728
PMID:25637637
Abstract

AIMS

To study the immunoexpression of proteins related to the mitotic checkpoint (cell division cycle 20 (CDC20), mitotic arrest deficient 2 (MAD2)) and the mitotic spindle (Aurora-B) in patients with myelodysplastic syndrome (MDS).

METHODS

Protein expression was analysed in bone marrow tissue samples from 40 patients with MDS using immunohistochemistry. Prognostic markers (transfusion dependency, depth of cytopenias, chromosomal abnormalities and survival) were also studied.

RESULTS

Higher MAD2 expression was observed among patients with platelets <50×10(9)/L than among patients with platelets ≥50×10(9)/L (42.6±22.8% vs 22.7±19.1%, respectively). Higher CDC20 expression was identified among patients with three dysplasias compared with patients who presented with one or two dysplasias (33.9±24.1% vs 10.5±5.7% vs 12.8±7.8%, respectively), among patients who exhibited a complex versus non-complex karyotype (50.0±30.2% vs 18.4±14%, respectively) and among patients with platelets <50×10(9)/L vs platelets ≥50×10(9)/L (38.2±26.2% vs 16.1±12.4%, respectively). Higher Aurora-B expression was found in patients with an abnormal versus normal karyotype (21.2±13.2% vs 7.5±5.0%, respectively). High expression of MAD2 and CDC20 (≥50%) was associated with severe thrombocytopenia. We also found statistically significant differences in the overall survival rate when comparing different degrees of CDC20, MAD2 and Aurora-B protein expression.

CONCLUSIONS

To the best of our knowledge, this is the first report to demonstrate that these proteins are associated with chromosomal abnormalities and poor prognosis in patients with MDS.

摘要

目的

研究骨髓增生异常综合征(MDS)患者中与有丝分裂检查点相关的蛋白质(细胞分裂周期蛋白20(CDC20)、有丝分裂阻滞缺陷蛋白2(MAD2))以及有丝分裂纺锤体(极光激酶B)的免疫表达情况。

方法

采用免疫组织化学方法分析40例MDS患者骨髓组织样本中的蛋白质表达。同时研究预后标志物(输血依赖性、血细胞减少程度、染色体异常和生存率)。

结果

血小板<50×10⁹/L的患者中MAD2表达高于血小板≥50×10⁹/L的患者(分别为42.6±22.8%和22.7±19.1%)。与有1种或2种发育异常的患者相比,有3种发育异常的患者中CDC20表达更高(分别为33.9±24.1%、10.5±5.7%和12.8±7.8%),核型复杂的患者与核型不复杂的患者相比CDC20表达更高(分别为50.0±30.2%和18.4±14%),血小板<50×10⁹/L的患者与血小板≥50×10⁹/L的患者相比CDC20表达更高(分别为38.2±26.2%和16.1±12.4%)。核型异常的患者中极光激酶B表达高于核型正常的患者(分别为21.2±13.2%和7.5±5.0%)。MAD2和CDC20高表达(≥50%)与严重血小板减少有关。比较不同程度的CDC20、MAD2和极光激酶B蛋白表达时,我们还发现总生存率存在统计学显著差异。

结论

据我们所知,这是第一份证明这些蛋白质与MDS患者染色体异常和预后不良相关的报告。

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