Evidence map›Paper›PMID 40938978›Full record

ArticleScience advances2025

CLL to Richter syndrome: Integrating network strategies with experiments elucidating disease drivers and personalized therapies.

Julia Maier, Julian D Schwab, Silke D Werle, Ralf Marienfeld, Stephan Stilgenbauer, Peter Möller, Nensi Ikonomi, Hans A Kestler

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Julia MaierInstitute of Medical Systems Biology, Ulm University, 89081 Ulm, Germany.ORCID 0000-0003-1577-7931
Julian D SchwabInstitute of Medical Systems Biology, Ulm University, 89081 Ulm, Germany.ORCID 0000-0002-3050-0618
Silke D WerleInstitute of Medical Systems Biology, Ulm University, 89081 Ulm, Germany.ORCID 0000-0002-5153-0269
Ralf MarienfeldInstitute of Pathology, University Hospital of Ulm, 89081 Ulm, Germany.ORCID 0000-0002-1309-1429
Stephan StilgenbauerComprehensive Cancer Center Ulm, University Hospital Ulm, 89081 Ulm, Germany.
Peter MöllerInstitute of Pathology, University Hospital of Ulm, 89081 Ulm, Germany.
Nensi IkonomiInstitute of Medical Systems Biology, Ulm University, 89081 Ulm, Germany.ORCID 0000-0003-0780-5832
Hans A KestlerInstitute of Medical Systems Biology, Ulm University, 89081 Ulm, Germany.ORCID 0000-0002-4759-5254

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic lymphocytic leukemia (CLL) is a common neoplasm that carries the risk of transformation into Richter's syndrome (RS), a highly aggressive B cell lymphoma with poor prognosis. Limited availability of animal models and cell lines hinders understanding of transformation mechanisms. Addressing this gap, we established the first in silico dynamic model of the disease. Our methodology integrates mathematical logic modeling with experimental data to identify disease drivers, mechanisms, and potential therapeutic targets. We validated the model by comparing the model's readout with experimental data from different biological levels, such as single-cell RNA sequencing analyses and a CLL/RS patient formalin-fixed paraffin-embedded (FFPE) tissue cohort. Our analyses identified BMI1 proto-oncogene and TP53 loss as key RS progression regulators. In addition, we performed an in silico target screening to identify promising target combinations in a personalized fashion. Through the synergy of mathematical modeling with experimental readouts, our model provides a complementary approach to investigate the process of CLL transformation to RS.

Indexed as

Leukemia, Lymphocytic, Chronic, B-CellPrecision MedicineComputer SimulationHumansProto-Oncogene MasSingle-Cell AnalysisTumor Suppressor Protein p53MAS1 protein, humanProto-Oncogene MasTumor Suppressor Protein p53

Identifiers

PMID40938978
PMCPMC12428933

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Registered trials

None linked

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.