Evidence map›Paper›PMID 33615197›Full record

ArticleiScience2021

Rituximab and obinutuzumab differentially hijack the B cell receptor and NOTCH1 signaling pathways.

Jennifer Edelmann, Arran D Dokal, Emma Vilventhraraja, Karlheinz Holzmann, David Britton, Tetyana Klymenko, Hartmut Döhner, Mark Cragg, Andrejs Braun, Pedro Cutillas and 1 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 14% of its field
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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

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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

11 authors at 4 institutions in 2 countries.

Jennifer EdelmannCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Arran D DokalCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Emma VilventhrarajaCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Karlheinz HolzmannCenter for Clinical Research, Genomics Core Facility, Ulm University, Helmholtzstr. 8/1, 89081 Ulm, Germany.
David BrittonCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Tetyana KlymenkoCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Hartmut DöhnerDepartment of Internal Medicine III, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Mark CraggAntibody and Vaccine Group, Centre for Cancer Immunology, University of Southampton Faculty of Medicine, Tremona Road, Southampton, SO16 6YD, UK.
Andrejs BraunCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Pedro CutillasCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
John G GribbenCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Queen Mary University of London · GBHelmholtz-Institute Ulm · DEUniversität Ulm · DEUniversity of Southampton · GB

Funding

Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
Cancer Research UK 24721NCI NIH HHS P01 CA081534
6 · The paper itself

Abstract

The anti-CD20 monoclonal antibodies rituximab and obinutuzumab differ in their mechanisms of action, with obinutuzumab evoking greater direct B cell death. To characterize the signaling processes responsible for improved B cell killing by obinutuzumab, we undertook a phosphoproteomics approach and demonstrate that rituximab and obinutuzumab differentially activate pathways downstream of the B cell receptor. Although both antibodies induce strong ERK and MYC activation sufficient to promote cell-cycle arrest and B cell death, obinutuzumab exceeds rituximab in supporting apoptosis induction by means of aberrant SYK phosphorylation. In contrast, rituximab elicits stronger anti-apoptotic signals by activating AKT, by impairing pro-apoptotic BAD, and by releasing membrane-bound NOTCH1 to up-regulate pro-survival target genes. As a consequence, rituximab appears to reinforce BCL2-mediated apoptosis resistance. The unexpected complexity and differences by which rituximab and obinutuzumab interfere with signaling pathways essential for lymphoma pathogenesis and treatment provide important impetus to optimize and personalize the application of different anti-CD20 treatments.

Indexed as

cancerimmunologysystems biology: proteomics

Identifiers

PMID33615197
PMCPMC7878992
OpenAlexW3124270842

What OpenQuestion 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 OpenQuestion graph.