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CEBPA 和 c-MYC 基因表达水平与急性髓细胞白血病发病机制和发展的关系。

Association between the CEBPA and c-MYC genes expression levels and acute myeloid leukemia pathogenesis and development.

机构信息

Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1 Street, 90-151, Lodz, Poland.

Department of Hematology, Institute of Hematology and Transfusion Medicine, Chocimska 5 Street, 00-791, Warsaw, Poland.

出版信息

Med Oncol. 2020 Nov 10;37(12):109. doi: 10.1007/s12032-020-01436-z.

Abstract

CEBPA and c-MYC genes belong to TF and play an essential role in hematologic malignancies development. Furthermore, these genes also co-regulate with RUNX1 and lead to bone marrow differentiation and may contribute to the leukemic transformation. Understanding the function and full characteristics of selected genes in the group of patients with AML can be helpful in assessing prognosis, and their usefulness as prognostic factors can be revealed. The aim of the study was to evaluate CEBPA and c-MYC mRNA expression level and to seek their association with demographical and clinical features of AML patients such as: age, gender, FAB classification, mortality or leukemia cell karyotype. Obtained results were also correlated with the expression level of the RUNX gene family. To assess of relative gene expression level the qPCR method was used. The expression levels of CEBPA and c-MYC gene varied among patients. Neither CEBPA nor c-MYC expression levels differed significantly between women and men (p=0.8325 and p=0.1698, respectively). No statistically significant correlation between age at the time of diagnosis and expression of CEBPA (p=0.4314) or c-MYC (p=0.9524) was stated. There were no significant associations between relative CEBPA (p=0.4247) or c-MYC (p=0.4655) expression level and FAB subtype and mortality among the enrolled patients (p=0.5858 and p=0.8437, respectively). However, it was observed that c-MYC and RUNX1 expression levels were significantly positively correlated (rS=0.328, p=0.0411). Overall, AML pathogenesis involves a complex interaction among CEBPA, c-MYC and RUNX family genes.

摘要

CEBPA 和 c-MYC 基因属于 TF,在血液系统恶性肿瘤的发展中起重要作用。此外,这些基因还与 RUNX1 共同调节,导致骨髓分化,并可能有助于白血病转化。了解 AML 患者组中选定基因的功能和全部特征有助于评估预后,并且可以揭示它们作为预后因素的有用性。本研究的目的是评估 CEBPA 和 c-MYC mRNA 的表达水平,并寻找它们与 AML 患者的人口统计学和临床特征(年龄、性别、FAB 分类、死亡率或白血病细胞核型)的关联。获得的结果还与 RUNX 基因家族的表达水平相关。为了评估相对基因表达水平,使用了 qPCR 方法。CEBPA 和 c-MYC 基因的表达水平在患者之间存在差异。CEBPA 和 c-MYC 的表达水平在女性和男性之间没有显著差异(分别为 p=0.8325 和 p=0.1698)。诊断时年龄与 CEBPA(p=0.4314)或 c-MYC(p=0.9524)表达之间没有统计学上的显著相关性。在纳入的患者中,相对 CEBPA(p=0.4247)或 c-MYC(p=0.4655)表达水平与 FAB 亚型和死亡率之间没有显著关联(分别为 p=0.5858 和 p=0.8437)。然而,观察到 c-MYC 和 RUNX1 表达水平呈显著正相关(rS=0.328,p=0.0411)。总体而言,AML 的发病机制涉及 CEBPA、c-MYC 和 RUNX 家族基因之间的复杂相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdc/7655568/04b6c3e3b6eb/12032_2020_1436_Fig1_HTML.jpg

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