ArticleTranslational cancer research2026
Single-cell analysis of UNC13D-mediated immune and dedifferentiation heterogeneity in acute myeloid leukemia and development of a prognostic model.
Article in Translational cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy, with its pathogenesis closely associated with cellular states at various stages of differentiation. Existing clinical prognostic models often fail to account for this heterogeneity and lack integration of key molecular pathways. This study aimed to characterize AML differentiation-associated heterogeneity at the single-cell level, investigate the role of UNC13D in immune and dedifferentiation states, and develop a prognostic model integrating these features. Methods: This study combined single-cell RNA sequencing data (GSE178910) with bulk RNA-sequencing (RNA-seq) datasets [The Cancer Genome Atlas-Acute Myeloid Leukemia (TCGA-LAML) and Oregon Health & Science University (OHSU)]. Seurat and Harmony were used for batch correction and unsupervised clustering, followed by cell state annotation using AddModuleScore-based scoring of lineage-specific gene sets. UNC13D expression was assessed to infer its association with differentiation stage and pathway activity. Prognostic genes within the MYC proto-oncogene signaling pathway were identified using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression. An eight-gene risk model was then constructed and validated across two cohorts. Results: We identified eleven AML cellular subpopulations, grouped into five functional differentiation states. UNC13D was predominantly expressed in common myeloid progenitor-like (CMP-like) cells and correlated with multiple oncogenic and immune-related pathways. The resulting eight-gene prognostic model ( Conclusions: Our study delineates the differentiation landscape of AML and identifies UNC13D as a potential biomarker of cellular plasticity and immune modulation. The constructed model provides a reliable prognostic tool and offers novel insights for AML stratification and precision therapy development.
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