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December 8, 2025BloodOpen Access

Acquisition of CLL-like epigenetic and transcriptomic states in low-count MBL

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Authors

SFStacey M. FernandesANAdi NaglerDDDavid M. Dorfman

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Overview

Randomised analysis reveals clonal dynamics and epigenetic states in low-count MBL, suggesting targets for prevention of CLL.

Key Points

  • This research aims to uncover the molecular events leading to chronic lymphocytic leukemia (CLL) from low-count monoclonal B cell lymphocytosis (LC-MBL).
  • Performed multi-modal single cell analysis on 34 peripheral blood samples from individuals with LC-MBL, HC-MBL, and CLL.
  • Integrated transcriptomic, epigenetic, and surface marker profiling with B cell receptor sequencing and copy number variation analysis.
  • Mapped transcriptional and epigenetic states using scRNA-seq and scATAC-seq profiles.
  • LC-MBL showed heterogeneous gene regulatory and expression states with early clonal dominance.
  • CLL-like epigenetic states were detectable at LC-MBL stage, indicating shifts in gene expression and chromatin accessibility.
  • Analysis identified distinct transcription factor activity related to B cell development and 'stemness' across LC-MBL and CLL.

Cite This Study

Fernandes et al. (2025) studied this question.

synapsesocial.com/papers/69362f4e4fa91c937236d834https://doi.org/10.1182/blood-2025-3876
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Single-cell epigenetic and transcriptomic states across the continuum of monoclonal B cell lymphocytosis to chronic lymphocytic leukemia2026 · 1 citations
  2. 2Mechanisms of Clonal Expansion: Mutations, Methylation, and ncRNA Networks From Monoclonal B‐Cell Lymphocytosis to Chronic Lymphocytic Leukemia2026
  3. 3Normal B Cells in MBL follow divergent maturation pathways that correlate with the IGHV mutation status of the pre-leukemic clone2025 · 1 citations
  4. 4Evaluation framework for monoclonal B-cell lymphocytosis.2026
  5. 5Single-cell chromatin profiling reveals early epigenetic reprogramming, subtype-specific regulatory networks, and JAK/STAT–IRF vulnerabilities in high-risk chronic myeloid leukemia2025