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PPP2R5C基因表达对细胞遗传学正常的成人急性髓系白血病患者的预后影响

Prognostic Impact of PPP2R5C Gene Expression in Adult Acute Myeloid Leukemia Patients with Normal Cytogenetics.

作者信息

El Taweel Maha, Gawdat Rania M, Abdelfattah Rafaat

机构信息

1Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

2Clinical and Chemical Pathology Department, Faculty of Medicine, Beni-Suef Teaching Hospital, Beni-Suef University, Beni- Suef, Egypt.

出版信息

Indian J Hematol Blood Transfus. 2020 Jan;36(1):37-46. doi: 10.1007/s12288-019-01142-5. Epub 2019 Jun 8.

Abstract

Protein Phosphatase 2A (PP2A) is a crucial regulator of the cellular signalling pathways, proliferation, cell cycle checkpoints and apoptosis. The PPP2R5C gene encodes PP2A regulatory B56γ subunit. Malignant transformation may occur, if mRNA of PPP2R5C is functionally deregulated, structurally altered, decreased or overexpressed. Therefore, the purpose of the study was to examine PPP2R5C mRNA expression, evaluate its association with the different clinical and haematological parameters and determine its prognostic impact in Egyptian adult acute myeloid leukaemia patients with normal cytogenetics (CN-AML). Peripheral blood samples of 50 de novo CN-AML patients and 20 age- and gender-matched healthy controls were examined for PPP2R5C expression by Quantitative Real Time-Polymerase Chain Reaction. The expression levels of PPP2R5C mRNA were significantly higher in the CN-AML samples than in the control samples ( ≤ 0.001). There was a statistical significant difference between the low and high expression levels of PPP2R5C with regard to age ( = 0.005,  = - 0.447,  = 0.001). The patients with an unfavourable response to induction chemotherapy had significant higher PPP2R5C expression levels than those with a favourable response ( = 0.002). There was a significant influence of high PPP2R5C expression levels on the overall survival and progression free survival ( = 0.03, 0.026), respectively. PPP2R5C overexpression is an adverse prognostic factor which affects leukaemogenesis in the CN-AML, it may predict the disease progression and overall survival during the follow-up of the patients.

摘要

蛋白磷酸酶2A(PP2A)是细胞信号通路、增殖、细胞周期检查点和细胞凋亡的关键调节因子。PPP2R5C基因编码PP2A调节性B56γ亚基。如果PPP2R5C的mRNA在功能上失调、结构改变、减少或过表达,可能会发生恶性转化。因此,本研究的目的是检测PPP2R5C mRNA的表达,评估其与不同临床和血液学参数的关联,并确定其对埃及正常细胞遗传学的成人急性髓系白血病患者(CN-AML)的预后影响。通过定量实时聚合酶链反应检测了50例初发CN-AML患者和20例年龄及性别匹配的健康对照者的外周血样本中PPP2R5C的表达。CN-AML样本中PPP2R5C mRNA的表达水平显著高于对照样本(≤0.001)。PPP2R5C低表达水平和高表达水平在年龄方面存在统计学显著差异(=0.005,=-0.447,=0.001)。诱导化疗反应不佳的患者PPP2R5C表达水平显著高于反应良好的患者(=0.002)。PPP2R5C高表达水平分别对总生存期和无进展生存期有显著影响(=0.03,0.026)。PPP2R5C过表达是影响CN-AML白血病发生的不良预后因素,它可能预测患者随访期间的疾病进展和总生存期。

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