Single-Cell Sequencing and Multi-Omic Technologies in Acute Myeloid Leukemia: A Literature Review

Abstract

Acute Myeloid Leukemia (AML) exemplifies leukemogenesis as a multistep process in which healthy hematopoietic stem
and progenitor cells (HSPCs) acquire sequential genetic and molecular alterations, leading to malignant transformation.
Traditional bulk sequencing approaches, although informative, cannot resolve the extensive cellular heterogeneity within
AML. The application of single-cell RNA sequencing (scRNA-seq)—as shown by Wu et al.—enables the identification of
distinct differentiation pathways and gene expression profiles at the individual cell level, which are specific to AML subtypes
and relate to disease progression. When combined with advanced surface proteomics techniques such as Cellular Indexing of
Transcriptomes and Epitopes by sequencing (CITE-seq), single-cell profiling offers comprehensive insights into AML’s
cellular architecture, revealing cell surface markers linked to proliferation, migration, and treatment resistance. Integration of
multi-omic layers—including transcriptomic, epigenomic, and proteomic data—has been further advanced in chromatin
accessibility profiling, collectively aiding in the discovery of innovative therapeutic targets and enhancing diagnostic
strategies. Comprehensive literature searches across PubMed, Cochrane, and Google Scholar were performed to select studies
on single-cell and multi-omic analyses in human AML, focusing on work published from 2014 onward. Studies emphasizing
leukemic subtypes, differentiation pathways, and novel therapeutic targets were prioritized, with particular attention to recent
conceptual and technological advancements in AML research. Recent work by Clark et al. and others has uncovered
previously unrecognized AML subpopulations with unique differentiation states and genetic alterations implicated in disease
progression and therapy resistance. The integration of transcriptomic and epigenomic data has clarified molecular pathways
and transcriptional regulators key to leukemic cell survival and proliferation. These advances have substantially deepened our
understanding of AML cellular heterogeneity, providing new insight into the mechanisms behind disease evolution and
treatment response. The application of single-cell and multi-omic approaches in AML marks a pivotal advance toward
personalized medicine. By enabling the identification of AML subtypes, refining risk stratification, and supporting real-time
disease monitoring, these technologies now facilitate the development of targeted therapies tailored to individual molecular
profiles, ultimately improving patient outcomes and guiding clinical decision-making.