Decoding leukemia at the single-cell level: clonal architecture, classification, microenvironment, and drug resistance

Abstract Leukemias are refractory hematological malignancies, characterized by marked intrinsic heterogeneity which poses significant obstacles to effective treatment. However, traditional bulk sequencing techniques have not been able to effectively unravel the heterogeneity among individual tumor cells. With the emergence of single-cell sequencing technology, it has bestowed upon us an unprecedented resolution to comprehend the mechanisms underlying leukemogenesis and drug resistance across various levels, including the genome, epigenome, transcriptome and proteome. Here, we provide an overview of the currently prevalent single-cell sequencing technologies and a detailed summary of single-cell studies conducted on leukemia, with a specific focus on four key aspects: (1) leukemia’s clonal architecture, (2) frameworks to determine leukemia subtypes, (3) tumor microenvironment (TME) and (4) the drug-resistant mechanisms of leukemia. This review provides a comprehensive summary of current single-cell studies on leukemia and highlights the markers and mechanisms that show promising clinical implications for the diagnosis and treatment of leukemia.