Tumor Heterogeneity in Leukemia and Lymphoma: Insights from Single-Cell Analyses
DOI:
https://doi.org/10.64229/fxex4a63Keywords:
Tumor Heterogeneity, Single-Cell Rna Sequencing, Leukemia, Lymphoma, Clonal Evolution, Tumor Microenvironment, Therapy Resistance, Minimal Residual DiseaseAbstract
Tumor heterogeneity is a fundamental property of leukemia and lymphoma that drives disease progression, relapse, and therapy resistance. For decades, bulk genomic and transcriptomic analyses have provided a foundational understanding of these malignancies but have obscured the cellular diversity within the tumor ecosystem. The advent of high-throughput single-cell technologies, particularly single-cell RNA sequencing (scRNA-seq), has revolutionized our capacity to deconvolute this complexity. This review synthesizes how single-cell analyses are reshaping our understanding of tumor heterogeneity in hematological cancers. We explore the role of intra-clonal genetic diversity in Acute Myeloid Leukemia (AML) and B-cell Acute Lymphoblastic Leukemia (B-ALL), the functional and transcriptional plasticity of subpopulations, and the dynamic interplay between malignant cells and the immune microenvironment in both leukemia and lymphoma. We further highlight how the tumor microenvironment in lymphomas fosters heterogeneity and immune evasion. Furthermore, the integration of single-cell data with spatial transcriptomics and computational models is beginning to predict evolutionary trajectories, offering a window into future clinical behaviors. Critically, we discuss how single-cell approaches have identified pre-existing or emergent resistant subclones under therapeutic pressure, providing a mechanistic basis for treatment failure. The clinical implications are profound, paving the way for single-cell diagnostics for minimal residual disease (MRD) monitoring and the identification of novel therapeutic targets. We conclude that single-cell multi-omics is an indispensable tool for unraveling the multifaceted nature of tumor heterogeneity, with the potential to propel the field toward more precise and effective therapeutic strategies.
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