High expression of malic enzyme 1 predicts adverse prognosis in patients with cytogenetically normal acute myeloid leukaemia and promotes leukaemogenesis through the IL-6/JAK2/STAT3 pathways

Progress in improving risk stratification

Elevated ME1 expression serves as an indicator of poorer prognosis in patients with CN-AML, potentially facilitating leukaemogenesis through the IL-6/JAK2/STAT3 pathway. This suggests that ME1 could be a promising prognostic biomarker and therapeutic target for CN-AML.

Gene expression and clinical data of patients with CN-AML were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, which were subjected to analysis. The prognostic significance of ME1 was assessed through Kaplan-Meier survival analysis, as well as univariate and multivariate Cox regression analyses. A novel risk model based on ME1 expression levels was developed using TCGA data for predicting CN-AML prognosis. Furthermore, the impact of ME1 silencing on AML cell lines was investigated using the Cell Counting Kit-8 assay and flow cytometry. Gene set enrichment analysis (GSEA) analysis and Western blotting were performed to explore the mechanism of ME1 in CN-AML.

CN-AML patients expressing higher ME1 levels exhibited shorter event-free survival (EFS) and overall survival (OS) compared to those with lower ME1 expression in the TCGA and multiple GEO datasets (all p < 0.05). Univariate and multivariate Cox regression analyses indicated that ME1 expression served as an independent prognostic factor for the EFS (p = 0.024 in TCGA, p = 0.035 in GSE6891) and OS (p = 0.039 in TCGA, p = 0.008 in GSE6891) in patients with CN-AML. The developed risk model demonstrated that patients with CN-AML in the high-risk group had worse survival than those in the low-risk group (hazard ratio: 2.67, 95% confidence interval: 1.54-4.65, p < 0.001) and exhibited strong predictive accuracy for 1-, 3- and 5-year OS (area under the curve = 0.69, 0.75, 0.79, respectively). ME1 knockdown significantly inhibited proliferation and increased apoptosis in AML cells (all p < 0.05). GSEA and Western blotting demonstrated that ME1 regulates the IL-6/JAK2/STAT3 pathway in CN-AML.