BACKGROUND Acute myeloid leukaemia (AML) is a malignant haematological tumour with high heterogeneity and mortality. A reliable prognostic assessment is critical for treatment strategies. However, the current prognostic evaluation system of AML is insufficient. METHODS Genome-wide univariate Cox regression analysis was performed on three independent AML datasets to screen for the prognostic-related genes. Kaplan-Meier survival analysis was employed to verify the efficacy of FHL1 in evaluating overall survival in 1298 de novo AML patients, 648 non-acute promyelocytic leukaemia AML patients and 407 cytogenetically normal AML patients; the data for some of these patients were also used for EFS and RFS validation. Multivariate Cox regression was performed to validate FHL1 as an independent prognostic indicator. WGCNA, GSEA, and gene correlation analysis were applied to explore the mechanism of FHL1 in AML. The synergistic cytocidal effect of FHL1 knockdown was verified in in vitro experiments. FINDINGS Comprehensive genome-wide analyses and large-sample validation showed that FHL1 is a powerful prognostic candidate for overall survival, event-free survival, and relapse-free survival in AML and is independent of prognosis-related clinical factors and genetic abnormalities. The molecular mechanism may occur through regulation of FHL1 in leukaemia stem cells, tumour-associated signalling pathways, and transmembrane transport of chemotherapeutic drugs. FHL1-targeted intervention enhances the sensitivity of AML cells to cytarabine. INTERPRETATION FHL1 may serve as an evaluation factor for clinical strategy selection, and its targeted intervention may be beneficial for chemotherapy in AML patients.

中文翻译：

---

FHL1在全基因组范围内的鉴定是急性髓细胞性白血病的有力预后对象和潜在治疗靶标。

背景技术急性髓细胞白血病（AML）是具有高异质性和高死亡率的恶性血液病。可靠的预后评估对于治疗策略至关重要。然而，目前的AML预后评估系统还不够。方法对三个独立的AML数据集进行全基因组单变量Cox回归分析，以筛选与预后相关的基因。Kaplan-Meier生存分析用于验证FHL1在评估1298例从头AML患者，648例非急性早幼粒细胞白血病AML患者和407例细胞遗传学正常的AML患者的总体生存中的有效性；这些患者中的一些患者的数据也用于EFS和RFS验证。进行多因素Cox回归以验证FHL1是独立的预后指标。WGCNA，GSEA，进行基因相关分析，探讨FHL1在AML中的作用机制。在体外实验中证实了FHL1敲除的协同杀细胞作用。结果全面的全基因组分析和大量样本验证表明，FHL1是AML总体生存期，无事件生存期和无复发生存期的强大预后候选者，并且与预后相关的临床因素和遗传异常无关。其分子机制可能是通过调节白血病干细胞中的FHL1，肿瘤相关的信号通路以及化学治疗药物的跨膜转运来实现的。FHL1靶向干预可增强AML细胞对阿糖胞苷的敏感性。解释FHL1可以作为临床策略选择的评估因素，