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.

白血病的特征之一是含有信号转导基因的多重重排和转录因子等非突变基因的过度表达。作为造血干细胞发育和红细胞生成的重要调节因子，LMO2 被认为是 T 细胞系中有效的致癌驱动因素，也是核型正常的 AML 患者预后不良的标志。 LDB1是LMO2诱导胸腺细胞转化为T-ALL的关键因子，并增强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。在此，敲除LMO2基因以观察其对NB4、Kasumi-1和K562细胞系的增殖、存活和集落形成的影响。使用质谱和 IP 实验，我们的结果表明 AML 细胞系中存在 LMO2/LDB1 蛋白复合物，这与之前的研究一致。此外，体外和体内实验表明LDB1对于AML细胞系的增殖和存活至关重要。 RNA-seq和ChIP-Seq结果分析表明LDB1可以调节凋亡相关基因，包括LMO2。在 LDB1 缺陷的 AML 细胞系中，LMO2 的过度表达部分补偿了增殖抑制。总之，我们的研究结果揭示了LDB1作为癌基因在AML中发挥着重要作用，并强调了LMO2/LDB1复合物在AML患者临床治疗中的潜在重要性。