ArticleBlood neoplasia2026
Single-cell sequencing reveals transcriptional and immunogenetic diversity in stereotyped chronic lymphocytic leukemia.
Article in Blood neoplasia, 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
Chronic lymphocytic leukemia (CLL) comprises immunogenetically defined stereotyped subsets of patients with distinct B-cell receptor (BcR) immunoglobulin features and clinical trajectories, yet the molecular pathways underlying subset-specific differences remain incompletely characterized. To resolve disease-relevant heterogeneity obscured in bulk analyses, we performed integrated single-cell transcriptomic and immunogenetic profiling of 48 557 malignant and bystander immune cells from 13 treatment-naïve primary patient samples representing poor-prognostic subsets #1 and #2 and the indolent subset #4. Despite interpatient variability, leukemic cells exhibited pronounced subset-specific transcriptional features, with enrichment of hypoxia-related genes in subset #1, oxidative phosphorylation (OXPHOS), MYC/E2F targets, and mechanistic target of rapamycin complex 1 (mTORC1) signaling in subset #2, and negative enrichment of hypoxia, apoptosis, and reactive oxygen species-related pathways in subset #4. Notably, compared with indolent subset #4, aggressive subsets #1 and #2 harbored increased proportions of metabolically active and recently emigrated/proliferative leukemic cells, characterized by a CXCR4
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