Journal Article

DKFZ-2026-00898

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Single-cell epigenetic and transcriptomic states across the continuum of monoclonal B cell lymphocytosis to chronic lymphocytic leukemia.

Rathgeber, A. C. ; Fernandes, S. M. ; Nagler, A. ; Li, S. ; Dorfman, D. M. ; Bullinger, L.DKFZ* ; Davids, M. S. ; Brown, J. R. ; Livak, K. J. ; Ludwig, L. S. ; Wu, C. J. ; Penter, L.DKFZ*

2026
BioMed Central London

Abstract: 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.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.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.

Keyword(s): Chronic lymphocytic leukemia ; Lineage-tracing ; Mitochondrial DNA mutations ; Monoclonal B cell lymphocytosis ; Multi-omics

Note: #DKTKZFB26# / #NCTZFB26# / 2026 Apr 15;27(1):175

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)
2. Koordinierungsstelle NCT Berlin (BR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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