Evidence map›Paper›PMID 41987205›Full record

ArticleGenome biology2026

Single-cell epigenetic and transcriptomic states across the continuum of monoclonal B cell lymphocytosis to chronic lymphocytic leukemia.

Anja C Rathgeber, Stacey M Fernandes, Adi Nagler, Shuqiang Li, David M Dorfman, Lars Bullinger, Matthew S Davids, Jennifer R Brown, Kenneth J Livak, Leif S Ludwig and 2 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Anja C RathgeberBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
Stacey M FernandesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Adi NaglerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Shuqiang LiTranslational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA.
David M DorfmanDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Lars BullingerDepartment of Hematology, Oncology, and Cancer Immunology, Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, Berlin, 13353, Germany.
Matthew S DavidsDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Jennifer R BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kenneth J LivakTranslational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA.
Leif S LudwigBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
Catherine J WuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Livius PenterDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. livius.penter@charite.de.ORCID http://orcid.org/0000-0002-9060-0207

Funding

ProteomicsP01CA206978 · NCI · DANA-FARBER CANCER INST · PI WU, CATHERINE JU-YING · 2016 to 2025
$17.0M
Optimizing novel agent combination therapy for previously untreated, high risk chronic lymphocytic leukemiaR01CA266298 · NCI · DANA-FARBER CANCER INST · PI MATTHEW S DAVIDS · 2022 to 2026
$2.0M
Single cell investigation of co-evolution in cancer cells and host cell immune microenvironmentR50CA251956 · NCI · DANA-FARBER CANCER INST · PI Shuqiang Li · 2020 to 2026
$1.4M
Brigitte und Dr. Konstanze Wegener-Stiftung A 2024 II (7)Deutsche Forschungsgemeinschaft LU 2336/10-1Else Kröner-Fresenius-Stiftung 2023_EKEA.102Leukemia and Lymphoma Society 5648-24NCI NIH HHS P01 CA206978NCI NIH HHS R01 CA266298NCI NIH HHS R50 CA251956NCI NIH HHS R50CA251956
6 · The paper itself

Abstract

backgroundChronic 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.

resultsUsing 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.

conclusionsThese results position LC-MBL as a key inflection point in early CLL pathogenesis and a potential target for progression risk prediction or preventive strategies.

Indexed as

B-LymphocytesEpigenesis, GeneticLeukemia, Lymphocytic, Chronic, B-CellLymphocytosisTranscriptomeDisease ProgressionDNA, MitochondrialHumansSingle-Cell AnalysisSingle-Cell Gene Expression AnalysisDNA, MitochondrialChronic lymphocytic leukemiaLineage-tracingMitochondrial DNA mutationsMonoclonal B cell lymphocytosisMulti-omics

Identifiers

PMID41987205
PMCPMC13192028

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.