Evidence map›Paper›PMID 39863584›Full record

ArticleNature communications2025

Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.

Lavinia Arseni, Gianluca Sigismondo, Haniyeh Yazdanparast, Johanne U Hermansen, Norman Mack, Sibylle Ohl, Verena Kalter, Murat Iskar, Mathias Kalxdorf, Dennis Friedel and 16 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Protein Profiles Predict Treatment Responses to the PI3K Inhibitor Umbralisib in Patients with Chronic Lymphocytic Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Trial
  2. Article
  3. Review
  4. Article
  5. Review
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

26 authors.

Lavinia Arseni *Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-5312-5278
Gianluca Sigismondo *Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center, Heidelberg, Germany.
Haniyeh YazdanparastDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Johanne U HermansenDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0003-3830-2277
Norman MackDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Sibylle OhlDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Verena KalterDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Murat IskarDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8603-4313
Mathias KalxdorfCellzome, a GSK Company, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-5266-0778
Dennis FriedelDivision of Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Mandy RettelEMBL, Proteomics Core Facility, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-8304-3385
Yashna PaulDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-2312-2954
Ingo RingshausenDepartment of Haematology, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.
Eric ElderingDepartment of Experimental Immunology, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-0561-6640
Julie DuboisDepartment of Hematology, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, Lymphoma and Myeloma Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Arnon P KaterDepartment of Hematology, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, Lymphoma and Myeloma Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-3190-1891
Marc ZapatkaDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8287-5967
Philipp M RoessnerDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Eugen TauschDivision of CLL, Department of Internal Medicine III, Ulm University, Ulm, Germany.
Stephan StilgenbauerDivision of CLL, Department of Internal Medicine III, Ulm University, Ulm, Germany.ORCID http://orcid.org/0000-0002-6830-9296
Sascha DietrichHeidelberg University, Department of Hematology, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-0648-1832
Mikhail M SavitskiEMBL, Proteomics Core Facility, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-2011-9247
Sigrid S SkånlandDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0003-1630-356X
Jeroen KrijgsveldDivision of Proteomics of Stem Cells and Cancer, German Cancer Research Center, Heidelberg, Germany.
Peter LichterDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Martina SeiffertDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany. m.seiffert@dkfz.de.ORCID http://orcid.org/0000-0001-5155-663X

Funding

José Carreras Leukämie-Stiftung (Deutsche José Carreras Leukämie-Stiftung) 03 R/2021
6 · The paper itself

Abstract

Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance. Preclinical treatment with the irreversible proteasome inhibitor carfilzomib administered upon ibrutinib resistance prolongs survival of mice. Longitudinal proteomic analysis of ibrutinib-resistant patients identifies deregulation in protein post-translational modifications. Additionally, cells from ibrutinib-resistant patients effectively respond to several proteasome inhibitors in co-culture assays. Altogether, our results from orthogonal omics approaches identify proteasome inhibition as potentially attractive treatment for chronic lymphocytic leukemia patients resistant or refractory to ibrutinib.

Indexed as

Drug Resistance, NeoplasmLeukemia, Lymphocytic, Chronic, B-CellOligopeptidesProteasome InhibitorsPyrazolesPyrimidinesAdenineAnimalsCell Line, TumorDisease Models, AnimalFemaleHumansMaleMicePiperidinesProteasome Endopeptidase ComplexAdeninecarfilzomibibrutinibOligopeptidesPiperidinesProteasome Endopeptidase ComplexProteasome InhibitorsPyrazolesPyrimidines

Identifiers

PMID39863584
PMCPMC11762753

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.