Yin Zhao, Li Fang, Zhou Qinjun, Zhu Jianfang, Liu Zhi, Huang Jing, Shen Huijuan, Ou Ruiming, Zhu Yangmin, Zhang Qing, Liu Shuang
Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, China.
Front Mol Biosci. 2022 Aug 15;9:959738. doi: 10.3389/fmolb.2022.959738. eCollection 2022.
Targeted therapy for acute myeloid leukemia (AML) is an effective strategy, but currently, there are very limited therapeutic targets for AML treatment. Ferroptosis is strongly related to drug resistance and carcinogenesis. However, there are few reports about ferroptosis in AML. This article explores the relationship between ferroptosis-related gene (FRG) expression and prognosis in AML patients from the FerrDb and the Cancer Genome Atlas (TCGA) databases. The ferroptosis-related gene ARNTL was observed to have high expression and poor prognosis in AML. Receiver operating characteristic curve (ROC) analysis revealed the predictive accuracy of the signature. The area under the time-dependent ROC curve (AUC) was 0.533 at one year, 0.619 at two years, and 0.622 at three years within the training cohort. Moreover, we found that the ARNTL expression is closely associated with tumor-infiltrating immune cells like the macrophages and NK cells. Inhibiting the ARNTL expression suppressed colony formation and induced ferroptosis in AML cells. Overall, the survival prediction model constructed based on ARNTL accurately predicted the survival in AML patients, which could be a potential candidate for diagnosing and treating AML.
急性髓系白血病（AML）的靶向治疗是一种有效的策略，但目前，用于AML治疗的治疗靶点非常有限。铁死亡与耐药性和致癌作用密切相关。然而，关于AML中铁死亡的报道很少。本文从FerrDb和癌症基因组图谱（TCGA）数据库中探讨了铁死亡相关基因（FRG）表达与AML患者预后之间的关系。观察到铁死亡相关基因ARNTL在AML中高表达且预后较差。受试者工作特征曲线（ROC）分析揭示了该特征的预测准确性。在训练队列中，时间依赖性ROC曲线（AUC）在1年时为0.533，2年时为0.619，3年时为0.622。此外，我们发现ARNTL表达与肿瘤浸润免疫细胞如巨噬细胞和NK细胞密切相关。抑制ARNTL表达可抑制AML细胞的集落形成并诱导铁死亡。总体而言，基于ARNTL构建的生存预测模型准确预测了AML患者的生存情况，这可能是诊断和治疗AML的潜在候选指标。
