LMO2 通过与转录共调控因子 LDB1 的相互作用促进AML的发展。
LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1.
发表日期：2023 Aug 12
作者：
Lihui Lu, Jianwei Wang, Fang Fang, Ailian Guo, Shuting Jiang, Yanfang Tao, Yongping Zhang, Yan Li, Kunlong Zhang, Zimu Zhang, Ran Zhuo, Xinran Chu, Xiaolu Li, Yuanyuan Tian, Li Ma, Xu Sang, Yanling Chen, Juanjuan Yu, Yang Yang, Haibo Cao, Jizhao Gao, Jun Lu, Shaoyan Hu, Jian Pan, Hailong He
来源：
Stem Cell Research & Therapy
摘要：
白血病的一个特点是它含有多种信号转导基因的重排和非突变基因的过度表达，如转录因子。作为造血干细胞发育和红细胞生成的重要调节因子，LMO2在T细胞系中被认为是有效的致癌驱动因子，并在具有正常染色体结构的急性髓系白血病患者中被视为不良预后标志物。LDB1是由LMO2引发的转化成为T-ALL的重要因子，并增强了白血病中致癌相关蛋白的稳定性。然而，LMO2和LDB1在AML中的功能和机制仍不清楚。因此，本研究通过抑制LMO2基因观察其对NB4、Kasumi-1和K562细胞株的增殖、存活和克隆形成的影响。通过质谱和IP实验，我们的结果显示了AML细胞株中存在LMO2/LDB1蛋白复合物，与以前的研究结果一致。此外，体外和体内实验揭示了LDB1对AML细胞株的增殖和存活至关重要。通过RNA-seq和ChIP-Seq结果的分析表明，LDB1可以调节与凋亡相关的基因，包括LMO2。在缺乏LDB1的AML细胞株中，LMO2的过表达部分弥补了增殖受抑制的情况。综上所述，我们的研究发现LDB1在AML中作为一个癌基因发挥着重要作用，并强调了LMO2/LDB1复合物在AML患者的临床治疗中的潜在重要性。 © 2023. 作者（们）。
One of the characteristics of leukemia is that it contains multiple rearrangements of signal transduction genes and overexpression of non-mutant genes, such as transcription factors. As an important regulator of hematopoietic stem cell development and erythropoiesis, LMO2 is considered an effective carcinogenic driver in T cell lines and a marker of poor prognosis in patients with AML with normal karyotype. LDB1 is a key factor in the transformation of thymocytes into T-ALL induced by LMO2, and enhances the stability of carcinogenic related proteins in leukemia. However, the function and mechanism of LMO2 and LDB1 in AML remains unclear. Herein, the LMO2 gene was knocked down to observe its effects on proliferation, survival, and colony formation of NB4, Kasumi-1 and K562 cell lines. Using mass spectrometry and IP experiments, our results showed the presence of LMO2/LDB1 protein complex in AML cell lines, which is consistent with previous studies. Furthermore, in vitro and in vivo experiments revealed that LDB1 is essential for the proliferation and survival of AML cell lines. Analysis of RNA-seq and ChIP-Seq results showed that LDB1 could regulate apoptosis-related genes, including LMO2. In LDB1-deficient AML cell lines, the overexpression of LMO2 partially compensates for the proliferation inhibition. In summary, our findings revealed that LDB1 played an important role in AML as an oncogene, and emphasize the potential importance of the LMO2/LDB1 complex in clinical treatment of patients with AML.© 2023. The Author(s).