KEY TAKEAWAYS
- The study aimed to investigate the prognostic significance of lysosome-related genes in patients with AML.
- Researchers noticed that lysosome-related gene signatures effectively predict AML prognosis.
Acute myeloid leukemia (AML) is a highly aggressive and pathogenic hematologic malignancy with consistently high mortality. Lysosomes are organelles involved in cell growth and metabolism that fuse to form specialized Auer rods in AML, and their role in AML has not been elucidated.
Peng Wan and the team aimed to identify AML subtypes centered on lysosome-related genes and to construct a prognostic model to guide individualized treatment of AML.
They performed an inclusive analysis using gene expression and clinical data from patients with AML, which were downloaded from 2 high-throughput sequencing platforms. The 191 lysosomal signature genes were obtained from the MsigDB database. Lysosomal clusters were identified through unsupervised consensus clustering. Subsequent analyses were conducted to examine the differences in molecular expression, biological processes, and the immune microenvironment among the identified lysosomal clusters.
Based on the molecular expression differences between these clusters, lysosomal-related genes impacting AML prognosis were screened using univariate and multivariate Cox regression analyses. LASSO regression algorithms were employed to construct prognostic models. The distribution of risk factors and Kaplan-Meier survival curves were applied to evaluate the survival distribution within the model.
Time-dependent ROC curves, nomograms, and calibration curves were used to assess the predictive performance of the prognostic models. TIDE scores and drug sensitivity analyses were utilized to explore the model’s implications for AML treatment.
About the study results, they identified 2 lysosomal clusters. Cluster 1 exhibited a longer survival time and stronger immune infiltration compared to Cluster 2. The differences in biological processes between the two lysosomal clusters were primarily observed in lysosomes, vesicles, immune cell function, and apoptosis. A prognostic model consisting of 6 prognosis-related genes was constructed, demonstrating good predictive performance across all 3 data sets.
Patients in the low-risk group survived significantly longer than those in the high-risk group and had higher immune infiltration and a stronger response to immunotherapy. High-risk patients showed greater sensitivity to cytarabine, imatinib, and bortezomib, but lower sensitivity to ATRA compared to low-risk patients.
The study concluded that the prognostic model based on lysosome-related genes can effectively predict the prognosis of patients with AML and provide valuable reference evidence for individualized immunotherapy and pharmacological chemotherapy for AML.
The study was funded by the Key Technology Innovation Special of Key Industries of the Chongqing Science and Technology Bureau, Joint Medical Research Project of Chongqing Municipal Science and Technology Commission and Health Commission, Chongqing Education Commission Science and Technology Research Program Project, and Chongqing Natural Science Foundation Project.
Source: https://pubmed.ncbi.nlm.nih.gov/38799454/
Wan P, Zhong L, Yu L, et al. (2024). “Lysosome-related genes predict acute myeloid leukemia prognosis and response to immunotherapy.” Front Immunol. 2024 May 10;15:1384633. doi: 10.3389/fimmu.2024.1384633. PMID: 38799454; PMCID: PMC11117069.
