Multiomics data integration of acute myeloid leukemia cases to identify immunogenic profiles
Year: 2025
Type: dissertation
Abstract: This study explores molecular mechanisms of 5-Azacytidine response in acute myeloid leukemia (AML) using an integrative multi-omics approach, combining data from whole exome sequencing (WES), RNA sequencing (RNA-seq), and neoantigen profiling. We aimed to characterize genetic mutations, transcriptional responses, and immunogenic profiles within AML patient clusters to identify potential biomarkers for predicting treatment efficacy. Samples were collected from patients before and 48 hours after 5-Azacytidine treatment, allowing for a comparative analysis of mutation and gene expression changes in response to therapy. In WES data, we identified distinct mutational landscapes in two patient clusters. Cluster A showed genetic patterns favoring apoptosis and absence of KIT mutations, indicating a possible predisposition to 5-Azacytidine responsiveness. In contrast, Cluster B displayed alterations in key oncogenes such as KIT, ATM, and GNAS, which may contribute to cellular survival mechanisms and potential therapy resistance. Transcriptomic analysis revealed enriched metabolic and cell survival pathways in Cluster B, suggesting adaptive responses that could undermine the efficacy of 5-Azacytidine as a single agent. By contrast, Cluster A’s transcriptional profile was associated with a more direct apoptotic response, aligning with its mutation profile. Neoantigen analysis further distinguished these clusters, with Cluster B showing a higher neoantigen load, suggesting an immunologically active environment that may enhance immune surveillance. This raises the potential for immunotherapy applications, particularly in Cluster B, where could complement 5-Azacytidine to overcome resistance mechanisms. The integration of WES, RNA-seq, and neoantigen data underscores the heterogeneity within AML and provides insight into stratified therapy. Cluster A, with its apoptotic gene signatures and lower neoantigen burden, may respond more favorably to 5-Azacytidine alone, while Cluster B could benefit from combined targeted and immune therapies to address its adaptive resistance profile. This research highlights the importance of comprehensive molecular profiling in AML and lays the foundation for personalized therapeutic approaches based.
Author: Angeli, Davide
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7077140917
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