Zhao Zhe, Wang Dongmei, Sheng Xue, Li Shuying, Liu Tingting, Chang Mengyuan, Feng Lei, Zhang Di, Ji Chunyan, Lu Fei, Ye Jingjing
Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.
Shandong Key Laboratory of Hematological Diseases and Immune Microenvironment, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Front Immunol. 2025 Jan 13;15:1429855. doi: 10.3389/fimmu.2024.1429855. eCollection 2024.
Basic leucine zipper ATF-like transcription factor (BATF) is a nuclear basic leucine zipper protein affiliated with the AP-1/ATF superfamily. Previous research has confirmed that BATF expression plays a significant role in the tumour microenvironment. However, the associations between BATF expression and prognoses in acute myeloid leukaemia (AML) patients and their immunological effects remain unclear.
Genomic and clinical AML data were got from the TCGA (TCGA-LAML) and GEO (GSE37642) databases for the subsequent analysis. The expression levels of BATF in AML patients were assessed using GEPIA, and the results were verified by qRT-PCR and Western blotting. In the meantime, the prognostic value of BATF was evaluated using univariate and multivariate analyses, receiver operating characteristic (ROC) curve (AUC) analysis, and Kaplan-Meier (KM) survival analysis. EdU, colony formation, and CCK-8 assays were employed to evaluate the proliferation of cells. Moreover, we detected the association of BATF expression with drug sensitivity through database analysis and experiments. To further investigate the mechanism of action of BATF in AML, RNA sequencing (RNA-seq) analysis was performed, followed by pathway enrichment analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Meanwhile, we detected the connection between BATF expression and the proportions of immune cells via flow cytometry in C1498 mouse model of AML. Finally, we investigated the association between BATF expression and cell-cell communication within the AML cell population using single-cell sequencing.
In this study, we thoroughly investigated the role of BATF in AML. First, we observed a significant elevation in the expression of BATF in patients and cells in AML. Further analysis revealed an association between high BATF expression and poor prognosis in AML. Additionally, BATF expression was found to promote the proliferative capacity of AML cells. Moreover, the results showed that the expression level of BATF dramatically affected the effect of chemotherapy in AML patients. We also discovered that BATF expression could activate multiple immune-related pathways, altering the proportions of CD8T cells and NK cells, suggesting that BATF may be a regulator of immune cell infiltration. Finally, there were differences in receptor ligand pairs between AML cells with high and low expression of BATF and immune cells.
Bioinformatics analysis and experimental verification revealed that BATF expression could alter the proportions of CD8T cells and NK cells in AML and affect drug sensitivity, making it a potential treatment target for AML.
碱性亮氨酸拉链ATF样转录因子（BATF）是一种隶属于AP-1/ATF超家族的核碱性亮氨酸拉链蛋白。先前的研究已证实BATF表达在肿瘤微环境中发挥重要作用。然而，BATF表达与急性髓系白血病（AML）患者预后及其免疫效应之间的关联仍不清楚。
从TCGA（TCGA-LAML）和GEO（GSE37642）数据库获取基因组和临床AML数据用于后续分析。使用GEPIA评估AML患者中BATF的表达水平，并通过qRT-PCR和蛋白质免疫印迹法进行验证。同时，使用单因素和多因素分析、受试者工作特征（ROC）曲线（AUC）分析以及Kaplan-Meier（KM）生存分析评估BATF的预后价值。采用EdU、集落形成和CCK-8实验评估细胞增殖。此外，我们通过数据库分析和实验检测BATF表达与药物敏感性的关联。为进一步探究BATF在AML中的作用机制，进行了RNA测序（RNA-seq）分析，随后使用京都基因与基因组百科全书（KEGG）通路分析进行通路富集分析。同时，我们在AML的C1498小鼠模型中通过流式细胞术检测BATF表达与免疫细胞比例之间的联系。最后，我们使用单细胞测序研究AML细胞群体中BATF表达与细胞间通讯的关联。
在本研究中，我们深入探究了BATF在AML中的作用。首先，我们观察到AML患者和细胞中BATF表达显著升高。进一步分析揭示了AML中BATF高表达与不良预后之间的关联。此外，发现BATF表达促进AML细胞的增殖能力。而且，结果表明BATF的表达水平显著影响AML患者的化疗效果。我们还发现BATF表达可激活多个免疫相关通路，改变CD8T细胞和NK细胞的比例，提示BATF可能是免疫细胞浸润的调节因子。最后，BATF高表达和低表达的AML细胞与免疫细胞之间的受体配体对存在差异。
生物信息学分析和实验验证表明，BATF表达可改变AML中CD8T细胞和NK细胞的比例并影响药物敏感性，使其成为AML的潜在治疗靶点。
