Abstract A050: Unraveling Immune Dysregulation in Acute Myeloid Leukemia: Insights from Whole Exome and Transcriptome Analysis

Abstract Background: Acute myeloid leukemia (AML) is characterized by uncontrolled proliferation of myeloid progenitor cells. This study aims to elucidate genetic and transcriptomic alterations in AML through whole exome sequencing (WES) and transcriptome analysis, linking these findings with regulatory networks in hematopoiesis and immunology. Methods: We performed WES and transcriptome analysis on 10 AML samples to identify genetic mutations and expression changes. Bioinformatics tools, including differential expression analysis, gene set enrichment analysis (GSEA), and pathway analysis, were used to identify critical genes and regulatory networks. Comparative analyses with hematopoietic stem cells (HSCs) and immune cell subsets were conducted. Single-cell RNA sequencing (scRNA-seq) data were analyzed to delineate cellular heterogeneity and lineage differentiation pathways affected in AML. Results: Integrative analysis revealed key transcription factors and epigenetic regulators, such as RUNX1, FLT3, CEBPA, TP53, WT-1, GATA2, and TET2, frequently mutated or dysregulated in AML. Differential expression analysis identified distinct gene expression signatures in AML cells compared to normal HSCs, highlighting disruptions in cell cycle regulation, differentiation, and apoptosis. Altered immune regulatory pathways, including IL-7R and PD-1, indicated disruptions in immune cell activation and homeostasis. Single-cell analysis highlighted the cellular diversity and plasticity in AML. Conclusion: Our integrative bioinformatics approach links genetic and transcriptomic alterations in AML with disruptions in hematopoiesis and immune function. Key regulators and pathways identified offer potential therapeutic targets and deepen understanding of AML pathogenesis. Citation Format: HARSH GOEL, Pranay Tanwar. Unraveling Immune Dysregulation in Acute Myeloid Leukemia: Insights from Whole Exome and Transcriptome Analysis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A050.