Prajapati Subhash C, Meydan Cem, Neelamraju Yaseswini, Wang Zhenjia, Fan Hao, Dunham Nicholas, Dillon Richard, Gandara Jorge A, Lee Tak, Sheridan Caroline, Zumbo Paul, Becker Michael W, Bullinger Lars, Carroll Martin P, D'Andrea Richard J, Levine Ross L, Mason Christopher, Melnick Ari M, Zang Chongzhi, Bekiranov Stefan, Garrett-Bakelman Francine E
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
bioRxiv. 2025 Aug 27:2025.08.25.670309. doi: 10.1101/2025.08.25.670309.
There is a continued need for identification of novel disease drivers of acute myeloid leukemia as many patients experience relapse and have poor clinical outcomes. Analyses from our study and publicly available datasets predicted CEBPD as a novel tumor suppressor gene in acute myeloid leukemia. Consistent with the analyses, CEBPD knockdown experiments showed activation of MAPK signaling with concomitant increase in cell growth rate, while upregulation experiments suggested induction of myeloid differentiation marker CD14 expression in AML cell lines OCI-AML2 and OCI-AML5. Consistent with a previous report, our genomics analyses and azacytidine treatment experiments suggested a role for DNA methylation in downregulation of CEBPD expression during AML pathogenesis. Altogether, our results provide experimental evidence for a tumor suppressor function of CEBPD in AML.
由于许多急性髓系白血病患者会复发且临床预后较差，因此持续需要鉴定该疾病的新型驱动因素。我们的研究分析以及公开可用数据集预测CEBPD是急性髓系白血病中的一种新型肿瘤抑制基因。与分析结果一致，CEBPD敲低实验显示MAPK信号激活，同时细胞生长速率增加，而上调实验表明在AML细胞系OCI-AML2和OCI-AML5中诱导髓系分化标志物CD14表达。与之前的报告一致，我们的基因组分析和阿扎胞苷治疗实验表明DNA甲基化在AML发病机制中CEBPD表达下调中起作用。总之，我们的结果为CEBPD在AML中的肿瘤抑制功能提供了实验证据。
