Abstract

Telomere maintenance is critical to ensure unlimited cancer cell proliferation, but the role of telomere-related genes in acute myeloid leukemia (AML) has not yet been thoroughly discussed. This study aims to develop a new prognostic risk model based on telomere-related genes and analyze potential mechanisms and targets. Cox regression analyses were used to build the prognostic risk model. Kaplan-Meier (KM) survival analysis and receiver operating characteristic (ROC) curve were used to assess the model performance. At the same time, we analyzed the relationship between the risk score and chemotherapy and immunotherapy and preliminarily explored possible mechanisms of immune resistance. The real-time polymerase chain reaction (PCR) was used to detect the prognosis gene expression levels. Finally, a prognostic signature of six telomere-related genes (TGPS6) including ALDH2, CDK18, DNMT3B, FRAT2, LGALSL, and RBL2 was constructed. The TGPS6 score was confirmed as an independent prognostic factor (HR 2.74, CI [2.13–3.53], p < 0.001) in AML and the five-year area under the ROC curve (AUC) value of the score in the training and validation set reached 0.74, 0.81 respectively. In addition, the TGPS6 perfected the European LeukemiaNet (ELN) 2017 prognosis risk stratification and performed well in both AML and cytogenetically normal AML (CN-AML) cohorts. The TGPS6 score also provided a reference for chemotherapy and immunotherapy in patients with AML.

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