Potential prognostic value and immune landscape of lactylation and liquid–liquid phase separation related genes in acute myeloid leukemia

Lactylation- and liquid-liquid phase separation-related differentially expressed genes (LLRDEGs) have been implicated in cancer. However, their role in acute myeloid leukemia (AML) remains largely unexplored. LLRDEGs associated with AML prognosis were identified using Cox regression and LASSO analyzes. A prognostic model based on three LLRDEGs was constructed for AML, and its associated biological functions were investigated. Furthermore, we evaluated differences in the tumor immune microenvironment based on this prognostic signature. This study represents the first comprehensive analysis of the prognostic value of LLRDEGs in AML patients, identifying three LLRDEGs with prognostic significance. A prognostic risk model was constructed using these three LLRDEGs, and its prognostic value was validated in an independent external AML dataset. This model was associated with the immune microenvironment of AML. Finally, we observed that chaperonin containing TCP1 subunit 5 (CCT5) was highly expressed in AML. In vitro experiments demonstrated that inhibition of CCT5 induces HL-60 cell cycle arrest and apoptosis. This research provides a theoretical basis relevant to AML treatment strategies. Acute myeloid leukemia (AML) is a severe type of blood cancer characterized by the rapid growth of abnormal white blood cells in the bone marrow, which hampers normal blood cell production. Despite advancements in treatment, the survival rates for AML patients, especially older adults, remain low. Understanding the molecular mechanisms behind AML could lead to better prognostic tools and treatments. This study explored the roles of specific genes related to lactylation and liquid–liquid phase separation (LLRDEGs) in AML. Researchers identified 11 LLRDEGs linked to AML prognosis and focused on three key genes (ALDH1A1, CCT5, and LAP3). They developed a prognostic model using these three genes and validated it with an independent dataset. The model effectively distinguished between high-risk and low-risk AML patients, indicating that those with higher expression of these genes had a worse prognosis. Additionally, the study examined differences in the tumor immune environment between high-risk and low-risk groups. This research provides a new prognostic model for AML based on three specific genes, offering a more precise method to predict patient outcomes. The study also highlights the connection between these genes and the immune environment in AML, which could guide future treatment strategies. Potentially improving survival rates and quality of life for those battling AML.

乳酰化与液液相分离相关差异表达基因（LLRDEGs）已被证实与癌症发生密切相关，但其在急性髓系白血病（AML）中的作用仍未得到充分探索。本研究通过Cox回归与最小绝对收缩和选择算子（LASSO）分析，筛选出与AML预后相关的LLRDEGs；构建了基于3个LLRDEGs的AML预后模型，并对其潜在生物学功能进行了探究；此外，基于该预后特征评估了肿瘤免疫微环境的差异。本研究首次全面分析了LLRDEGs在AML患者中的预后价值，最终筛选出3个具有预后意义的LLRDEGs。基于这3个基因构建的预后风险模型，在独立外部AML数据集上验证了其预后效能，且该模型与AML免疫微环境显著相关。最后，本研究发现TCP1伴侣蛋白复合物亚基5（CCT5）在AML中呈高表达；体外实验证实，抑制CCT5可诱导HL-60细胞发生周期阻滞与凋亡，本研究为AML治疗策略提供了理论依据。

急性髓系白血病（AML）是一种恶性血液系统肿瘤，以骨髓中异常白细胞快速增殖、正常造血功能受抑为主要特征。尽管治疗手段不断进步，AML患者（尤其是老年患者）的生存率仍处于较低水平。阐明AML发生的分子机制，有望开发更精准的预后评估工具与治疗方案。

本研究探讨了乳酰化与液液相分离相关差异表达基因（LLRDEGs）在AML中的作用：研究人员首先筛选出11个与AML预后相关的LLRDEGs，并聚焦于其中3个关键基因（ALDH1A1、CCT5及LAP3）；基于这3个基因构建了预后模型，并通过独立数据集完成验证。该模型可有效区分AML高危与低危患者，提示这3个基因高表达的患者预后更差。此外，本研究还分析了高危组与低危组患者的肿瘤免疫微环境差异。本研究基于3个特定基因构建了新型AML预后模型，为精准预测患者预后提供了更可靠的方法；同时揭示了这些基因与AML免疫微环境的关联，可为未来治疗策略的制定提供指导，有望改善AML患者的生存率与生存质量。