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| Item Type: | Article |
|---|---|
| Title: | Single-cell epigenetic and transcriptomic states across the continuum of monoclonal B cell lymphocytosis to chronic lymphocytic leukemia |
| Creators: |
Rathgeber, Anja C.  ORCID: https://orcid.org/0000-0003-3264-1040, Fernandes, Stacey M., Nagler, Adi, Li, Shuqiang, Dorfman, David M., Bullinger, Lars ORCID: https://orcid.org/0000-0002-5890-5510, Davids, Matthew S., Brown, Jennifer R., Livak, Kenneth J., Ludwig, Leif S. ORCID: https://orcid.org/0000-0002-2916-2164, Wu, Catherine J. and Penter, Livius ORCID: https://orcid.org/0000-0002-9060-0207
|
| Abstract: | BACKGROUND: Chronic lymphocytic leukemia (CLL) develops from physiologic B cells through low- and high-count monoclonal B cell lymphocytosis (LC-/HC-MBL). The timing and nature of early B cell expansion and molecular evolution remain unclear, limiting prediction of progression. RESULTS: Using multi-omics single-cell sequencing integrating chromatin accessibility, transcriptional, proteomic, and mitochondrial DNA (mtDNA) profiles across normal B cells, LC-/HC-MBL, and CLL, we delineate clonal relationships and evolutionary trajectories. Our data reveals subclonal, epigenetic, and transcriptomic stability during the transition from HC-MBL to CLL, suggesting a continuous disease spectrum rather than distinct evolutionary phases. CLL-like molecular states already exist in LC-MBL and, along with individual-specific heterogeneity across HC-MBL/CLL, are linked with disease progression. Finally, we find genetic evidence for a shared progenitor between physiologic and monoclonal B cells. CONCLUSIONS: These results position LC-MBL as a key inflection point in early CLL pathogenesis and a potential target for progression risk prediction or preventive strategies. |
| Keywords: | Monoclonal B Cell Lymphocytosis, Chronic Lymphocytic Leukemia, Mitochondrial DNA Mutations, Lineage-Tracing, Multi-Omics |
| Source: | Genome Biology |
| ISSN: | 1474-760X |
| Publisher: | BioMed Central |
| Volume: | 27 |
| Number: | 1 |
| Page Range: | 175 |
| Date: | 21 May 2026 |
| Additional Information: | Erratum in: Genome Biol 27(1):181. |
| Official Publication: | https://doi.org/10.1186/s13059-026-04072-4 |
| PubMed: | View item in PubMed |
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