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Esco2促进急性髓系白血病细胞增殖及存活的功能研究

李溥娇¹, 袁诗如², 孙国欢², 程辉^2,*

¹天津医科大学，细胞生态海河实验室，天津 300070；²北京协和医学院/中国医学科学院/血液学研究所/血液病医院血液与健康全国重点实验室，国家血液系统疾病临床医学研究中心，细胞生态海河实验室，天津 300020

摘要

本文旨在探讨Esco2在急性髓系白血病(acute myeloid leukemia, AML)中的表达特征及其对AML细胞生物学行为的影响。基于TCGA-LAML及GTEx数据库分析ESCO2 表达水平及其与AML患者预后的关系。用MLL-AF9 驱动的AML细胞构建sgRNA介导的Esco2 缺失模型，并通过体内、体外实验验证其功能。通过小鼠骨髓移植模型评估Esco2 缺失对白血病进展的影响；用集落形成实验、细胞增殖实验及Annexin V流式细胞术检测AML细胞生长和凋亡变化。同时用差异表达分析及基因集富集分析(gene set enrichment analysis, GSEA)探讨Esco2 相关通路。结果显示，与正常组织相比，ESCO2 在AML中显著高表达(P < 2.2 × 10⁻¹⁶)，且高表达与不良预后相关(P = 0.04)。Esco2 缺失显著延长受体小鼠生存期(P = 0.0227)并降低白血病负荷。体外实验显示，Esco2 缺失抑制AML细胞增殖和集落形成能力，并促进细胞凋亡。转录组分析及蛋白验证显示，Esco2 缺失上调AML细胞中E2F 转录因子1 (E2F transcription factor 1, E2F1)与细胞周期蛋白依赖性激酶抑制蛋白1A (cyclindependentkinase inhibitor 1A，Cdkn1a，又称 p21)表达，提示Esco2 参与细胞周期稳态调控并与细胞周期阻滞及凋亡进程相关。以上结果表明，Esco2 在AML中呈高表达状态，Esco2 缺失可显著抑制白血病细胞的增殖与存活，并延缓AML进展，提示Esco2 在AML发生、发展中具有重要生物学意义。

关键词： Esco2; 急性髓系白血病(AML); 细胞增殖; 细胞凋亡

Functional study of Esco2 in promoting proliferation and survival of acute myeloid leukemia cells

LI Pu-Jiao¹, YUAN Shi-Ru², SUN Guo-Huan², CHENG Hui^2,*

¹Haihe Laboratory of Cell Ecosystem, Tianjin Medical University, Tianjin 300070, China；²National Key Laboratory of Blood Science, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China

Abstract

The present study aimed to investigate the expression pattern of Esco2 in acute myeloid leukemia (AML) and its role in regulating the biological behavior of AML cells. The expression level of ESCO2 and its association with prognosis in patients with AML were analyzed using the TCGA-LAML and GTEx datasets. An sgRNA-mediated Esco2 depletion model was established in MLL-AF9-driven AML cells, and its function was validated through both in vitro and in vivo experiments. A murine bone marrow transplantation model was used to evaluate the effects of Esco2 depletion on leukemia progression. Colony formation assay, cell proliferation assay, and Annexin V-based flow cytometry were performed to assess AML cell growth and apoptosis. Differential gene expression analysis and gene set enrichment analysis (GSEA) were conducted to explore Esco2-related pathways. The results showed that, compared with normal tissues, ESCO2 was significantly up-regulated in AML (P < 2.2 × 10-16), and high expression was significantly associated with poor prognosis (P = 0.04). Esco2 depletion markedly prolonged the survival of recipient mice (P = 0.0227) and reduced leukemic burden. In vitro experiments showed that Esco2 depletion suppressed proliferation and colony-forming capacity of AML cells and promoted apoptosis. Transcriptomic and Western blot analyses revealed that Esco2 depletion up-regulated the expression of E2F transcription factor 1 (E2F1) and cyclin-dependent kinase inhibitor 1A (Cdkn1a, p21) in AML cells, suggesting that Esco2 might be involved in cell cycle homeostasis and associated with cell cycle arrest and apoptosis. These results suggest that Esco2 is highly expressed in AML, whereas Esco2 depletion significantly suppresses leukemic cell proliferation and survival and delays AML progression, indicating its important biological significance in the occurrence and development of AML.

Key words: Esco2; acute myeloid leukemia (AML); cell proliferation; cell apoptosis

收稿日期：　　录用日期：

通讯作者：程辉　　E-mail:

DOI: 10.13294/j.aps.2026.0055

引用本文：

李溥娇, 袁诗如, 孙国欢, 程辉. Esco2促进急性髓系白血病细胞增殖及存活的功能研究[J]. 生理学报 2026; 78 (4): 921-930.

LI Pu-Jiao, YUAN Shi-Ru, SUN Guo-Huan, CHENG Hui. Functional study of Esco2 in promoting proliferation and survival of acute myeloid leukemia cells. Acta Physiol Sin 2026; 78 (4): 921-930 (in Chinese with English abstract).