https://orcid.org/0000-0002-7598-9584
Key Points
A comprehensive prognostic model of 69 lncRNAs was generated to predict RFS in pedAML and further refining the current risk stratification
A nomogram incorporating the 69 lncRNAs signature, NPM mutation and WBC was developed to stratify patients into relapse-risk groups
Risk stratification using genetics and minimal residual disease (MRD) has allowed to increase the cure rates of pediatric acute myeloid leukemia (pedAML) up to 70% in contemporary protocols. Nevertheless, approximately 30% of patients still experience relapse, indicating a need to optimize stratification strategies. Recently, long non-coding RNA (lncRNA) expression has been shown to hold prognostic power in multiple cancer types. Here, we aimed at refining relapse prediction in pedAML using lncRNA expression. We built a relapse-related lncRNA prognostic signature, named AMLlnc69, using 871 pedAML patients transcriptomes obtained from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) repository. We identified a 69 lncRNA signature AMLlnc69 that is highly predictive of relapse-risk (c-index = 0.73), with area under the ROC curve (AUC) values for predicting the 1-, 2-, and 3-year relapse-free survival (RFS) of 0.78, 0.77, and 0.77, respectively. The internal validation using a bootstrap method (resampling times = 1000) resulted in a c-index of 0.72 and AUC values for predicting the 1-, 2-, and 3-year RFS of 0.77, 0.76, and 0.76, respectively. Through a Cox regression analysis, AMLlnc69, NPM mutation and WBC at diagnosis were identified as independent predictors of RFS. Finally, a nomogram was build using these two parameters, showing a c-index of 0.80 and 0.71 after bootstrapping (n =1000). In conclusion, the identified AMLlnc69 will, after prospective validation, add important information to guide management of pedAML patients. The nomogram is a promising tool for easy stratification of patients into a novel scheme of relapse-risk groups.
