Single-Cell and Spatial Omics in Hematopathology: From Cellular Heterogeneity to Precision Diagnostics

ABSTRACT:

Hematopathology has entered a new era with the emergence of single cell and spatial omics technologies, which provide unprecedented resolution for investigating cellular heterogeneity, clonal evolution, and tissue organization. Conventional diagnostic approaches, including morphology, immunophenotyping, flow cytometry, and bulk molecular analysis, have substantially advanced the diagnosis of hematologic disorders but often fail to capture rare cell populations and complex microenvironmental interactions. Single cell transcriptomics, chromatin accessibility profiling, and multimodal omics enable comprehensive characterization of individual cells, while spatial omics preserves tissue architecture and reveals the spatial distribution of malignant and nonmalignant cell populations. Together, these technologies have expanded the understanding of disease biology in acute myeloid leukemia, myelodysplastic syndromes, lymphomas, and other hematologic malignancies by identifying novel cellular states, early progenitor abnormalities, mechanisms of treatment resistance, and biomarkers associated with disease progression and therapeutic response. Integration of single cell and spatial datasets has also provided detailed insights into bone marrow niche organization and tumor microenvironment dynamics. Although challenges related to cost, standardization, computational analysis, and clinical implementation remain, ongoing technological advances are expected to facilitate broader diagnostic applications. This review summarizes the principles of single cell and spatial omics, highlights major discoveries in hematologic malignancies, and discusses their potential to refine disease classification, improve prognostic assessment, and support precision diagnostics in hematopathology.

Keywords: Single cell omics; Spatial omics; Hematopathology; Acute myeloid leukemia; Myelodysplastic syndromes; Lymphoma; Precision diagnostics; Bone marrow microenvironmen