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初发急性髓系白血病患者中CCAAT/增强子结合蛋白(C/EBP)α(CEBPA)和 runt 相关转录因子 1(RUNX1)表达的评估

Evaluation of CCAAT/Enhancer Binding Protein (C/EBP) Alpha (CEBPA) and Runt-Related Transcription Factor 1 (RUNX1) Expression in Patients with De Novo Acute Myeloid Leukemia.

作者信息

Salarpour Fatemeh, Goudarzipour Kourosh, Mohammadi Mohammad Hossein, Ahmadzadeh Ahmad, Faraahi Sara, Farsani Mehdi Allahbakhshian

机构信息

Laboratory Hematology and blood Banking Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran.

Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.

出版信息

Ann Hum Genet. 2017 Nov;81(6):276-283. doi: 10.1111/ahg.12210. Epub 2017 Sep 11.

Abstract

The CCAAT/enhancer binding protein (C/EBP) alpha (CEBPA) and Runt-related transcription factor 1 (RUNX1) genes have been traditionally regarded as two essential genes involved in normal myeloid maturation. Although the link between mutations in these genes and the development of acute myeloid leukemia (AML) has been extensively documented, the ramifications of gene expression dysregulations of CEBPA and RUNX1 has drawn less attention. The present study investigated CEBPA and RUNX1 gene expression levels in 96 primary AML specimens against a normal control group by way of real-time RT-PCR. Our results reveal that CEBPA and RUNX1 gene expression levels were unexpectedly and significantly higher in patients with AML when compared to the levels detected in the normal control group (P < 0.0001). Furthermore, the correlation between CEBPA and RUNX1 was significant and positive (P-value: 0.011, r: 0.257). Our data contradicts the widely established role of CEBPA and RUNX1 in myeloid differentiation, as we saw lower levels of CEBPA and RUNX1 expression to be exhibited in patients with AML. Likely, our data demonstrates that higher levels of CEBPA and RUNX1 expression were closely correlated with reduced myeloid maturation, but this idea needs to approved. It suggests that despite the current established functions of genes involved in cell differentiation, the leukemogenesis process has the capability to transform normal hematopoietic precursors in a manner that may employ the differentiation related gene at the service of malignancy.

摘要

CCAAT/增强子结合蛋白(C/EBP)α(CEBPA)和 runt 相关转录因子 1(RUNX1)基因传统上被认为是参与正常髓系成熟的两个关键基因。尽管这些基因的突变与急性髓系白血病(AML)的发生之间的联系已有大量文献记载,但 CEBPA 和 RUNX1 基因表达失调的影响却较少受到关注。本研究通过实时 RT-PCR 检测了 96 例原发性 AML 标本中 CEBPA 和 RUNX1 基因的表达水平,并与正常对照组进行比较。我们的结果显示,与正常对照组检测到的水平相比,AML 患者中 CEBPA 和 RUNX1 基因的表达水平意外且显著升高(P < 0.0001)。此外,CEBPA 和 RUNX1 之间的相关性显著且呈正相关(P 值:0.011,r:0.257)。我们的数据与 CEBPA 和 RUNX1 在髓系分化中广泛确立的作用相矛盾,因为我们发现 AML 患者中 CEBPA 和 RUNX1 的表达水平较低。可能的是,我们的数据表明 CEBPA 和 RUNX1 的较高表达水平与髓系成熟降低密切相关,但这一观点需要得到证实。这表明尽管目前已确定参与细胞分化的基因的功能,但白血病发生过程有能力以一种可能利用与分化相关的基因来服务于恶性肿瘤的方式转化正常造血前体细胞。

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