Diving into the transcriptional landscape of leukemic stem cells in acute myeloid leukemia at single-cell resolution

PURPOSE: The aim of this review is to summarize transcriptomic studies using single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq to investigate leukemic stem cells (LSCs) population in acute myeloid leukemia (AML). METHODS: Literature for inclusion was identified through a PubMed search. Twenty-seven studies were analyzed, covering various aspects of LSCs biology, including epigenetic, transcriptional, and translational gene regulation, metabolic reprogramming or cellular differentiation. RESULTS: The reviewed studies highlight the complexity of LSCs, including their quiescent state, state-to-state cellular plasticity, and metabolic reprogramming from glycolysis to lipogenesis. Comparative analyses of matched diagnostic and post-treatment samples provide insights into the dynamic behavior of LSCs during therapy. The findings also identify potential therapeutic targets and strategies to selectively eradicate LSCs. CONCLUSION: Single-cell RNA sequencing technologies offer unprecedented resolution for studying LSCs in AML, revealing cellular heterogeneity and dynamic evolution within these critical populations. Despite these advances, standardized criteria for LSCs identification are still needed, and longitudinal studies at clinically relevant time points are essential to fully understand their role in disease progression and therapy resistance. Such approaches may ultimately uncover novel therapeutic vulnerabilities and improve clinical management of AML.