Evidence map›Paper›PMID 40498456›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Disruption of constitutive CXCR4 oligomers impairs oncogenic properties in lymphoid neoplasms.

Simon Mobach, Nick D Bergkamp, Ziliang Ma, Marco V Haselager, Stephanie M Anbuhl, Daphne Jurriens, Jelle van den Bor, Ziming Wang, Caitrin Crudden, Jamie L Roos and 12 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Regulation of CXCR4 function by S1PCell communication and signaling : CCS · 2025
    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

22 authors.

Simon Mobach *Department of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.ORCID 0000-0001-8320-214X
Nick D Bergkamp *Department of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.ORCID 0000-0001-5692-5975
Ziliang Ma *Department of Biomolecular Mass Spectrometry and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht 3584 CH, The Netherlands.ORCID 0000-0003-4285-6598
Marco V HaselagerAmsterdam University Medical Center location University of Amsterdam, Department of Hematology, Amsterdam 1105 AZ, The Netherlands.ORCID 0000-0002-1410-7285
Stephanie M AnbuhlDepartment of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.
Daphne JurriensCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, Netherlands.
Jelle van den BorDepartment of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.ORCID 0000-0002-2411-2379
Ziming WangReceptor Signaling Group, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
Caitrin CruddenDepartment of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.
Jamie L RoosAmsterdam University Medical Center location University of Amsterdam, Department of Hematology, Amsterdam 1105 AZ, The Netherlands.ORCID 0009-0004-4884-7726
Claudia V Perez AlmeriaDepartment of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.ORCID 0000-0002-7312-8529
Rick A BoergonjeDepartment of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.
Martin J LohseReceptor Signaling Group, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.ORCID 0000-0002-0599-3510
Reggie BosmaDepartment of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.
Eric ElderingLymphoma and Myeloma Center Amsterdam, Amsterdam 1105 AZ, The Netherlands.ORCID 0000-0003-0561-6640
Marco SideriusDepartment of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.ORCID 0000-0003-3630-4228
Wei WuDepartment of Biomolecular Mass Spectrometry and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht 3584 CH, The Netherlands.
Marcel SpaargarenLymphoma and Myeloma Center Amsterdam, Amsterdam 1105 AZ, The Netherlands.ORCID 0000-0002-3135-5109
Sanne H ToninoAmsterdam University Medical Center location University of Amsterdam, Department of Hematology, Amsterdam 1105 AZ, The Netherlands.
Arnon P KaterAmsterdam University Medical Center location University of Amsterdam, Department of Hematology, Amsterdam 1105 AZ, The Netherlands.
Martine J SmitDepartment of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.ORCID 0000-0003-2713-0238
Raimond HeukersDepartment of Chemistry and Pharmaceutical Sciences, Division of Medicinal Chemistry, Amsterdam Institute for Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands.ORCID 0000-0003-4498-7751

Funding

EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA) 641833-ONCORNETEC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA) 860229-ONCORNET 2.0Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) ENPPS.TA.019.003 MAGNETICZonMw (Netherlands Organisation for Health Research and Development) 09150162010212ZonMw (Netherlands Organisation for Health Research and Development) 91217002
6 · The paper itself

Abstract

The chemokine receptor CXCR4 is overexpressed in many cancers and contributes to pathogenesis, disease progression, and resistance to therapies. CXCR4 is known to form oligomers, but the potential functional relevance in malignancies remains elusive. Using a nanobody-based BRET method, we demonstrate that oligomerization of endogenous CXCR4 on lymphoid cancer cell lines correlates with enhanced expression levels. Specific disruption of CXCR4 oligomers reduced basal cell migration and prosurvival signaling via changes in the phosphoproteome, indicating the existence of constitutive CXCR4 oligomer-mediated signaling. Oligomer disruption also inhibited growth of primary CLL 3D spheroids and sensitized primary malignant cells to clinically used Bcl-2 inhibitor venetoclax. Given its limited efficacy in some patients and the ability to develop resistance, sensitizing malignant B cells to venetoclax is of clinical relevance. Taken together, we established a noncanonical and critical role for CXCR4 oligomers in lymphoid neoplasms and demonstrated that their selective targeting has clinical potential.

Indexed as

Leukemia, Lymphocytic, Chronic, B-CellReceptors, CXCR4CarcinogenesisCell Line, TumorCell MovementHumansProtein MultimerizationSignal TransductionCXCR4 protein, humanReceptors, CXCR4CXCR4drug sensitizationleukemiareceptor oligomerization

Identifiers

PMID40498456
PMCPMC12184429

What OpenQuestion holds

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Registered trials

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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.