Evidence map›Paper›PMID 22354003›Full record

ArticleBlood2012

Antibody-induced nonapoptotic cell death in human lymphoma and leukemia cells is mediated through a novel reactive oxygen species-dependent pathway.

Jamie Honeychurch, Waleed Alduaij, Mahsa Azizyan, Eleanor J Cheadle, Helene Pelicano, Andrei Ivanov, Peng Huang, Mark S Cragg, Tim M Illidge

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
8.0field-weighted citation impact, top 2% 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

59 citing papers in PubMed, 128 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Sequelae of B-Cell Depleting Therapy: An Immunologist's Perspective.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Targeting CD20: teaching an old dog new tricks.Hematology. American Society of Hematology. Education Program · 2019
    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

9 authors at 5 institutions in 2 countries.

Jamie HoneychurchTargeted Therapy Group, Paterson Institute for Cancer Research, School of Cancer and Enabling Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK.
Waleed Alduaij
Mahsa Azizyan
Eleanor J Cheadle
Helene Pelicano
Andrei Ivanov
Peng Huang
Mark S Cragg
Tim M Illidge
Cancer Research UK Manchester Institute · GBThe University of Texas MD Anderson Cancer Center · USCancer Research UK Scotland Institute · GBTenovus Cancer Care · GBUniversity of Manchester · GB

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Cancer Research UK 11335
6 · The paper itself

Abstract

Monoclonal antibodies (mAbs) have revolutionized the treatment of B-cell malignancies. Although Fc-dependent mechanisms of mAb-mediated tumor clearance have been extensively studied, the ability of mAbs to directly evoke programmed cell death (PCD) in the target cell and the underlying mechanisms involved remain under-investigated. We recently demonstrated that certain mAbs (type II anti-CD20 and anti-HLA DR mAbs) potently evoked PCD through an actin-dependent, lysosome-mediated process. Here, we reveal that the induction of PCD by these mAbs, including the type II anti-CD20 mAb GA101 (obinutuzumab), directly correlates with their ability to produce reactive oxygen species (ROS) in human B-lymphoma cell lines and primary B-cell chronic lymphocytic leukemia cells. ROS scavengers abrogated mAb-induced PCD indicating that ROS are required for the execution of cell death. ROS were generated downstream of mAb-induced actin cytoskeletal reorganization and lysosome membrane permeabilization. ROS production was independent of mitochondria and unaffected by BCL-2 overexpression. Instead, ROS generation was mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. These findings provide further insights into a previously unrecognized role for NADPH oxidase-derived ROS in mediating nonapoptotic PCD evoked by mAbs in B-cell malignancies. This newly characterized cell death pathway may potentially be exploited to eliminate malignant cells, which are refractory to conventional chemotherapy and immunotherapy.

Indexed as

ActinsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntigens, CD20ApoptosisCell DeathCell Line, TumorGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansLeukemiaLymphomaMembrane GlycoproteinsMitochondriaNADPH Oxidase 2NADPH OxidasesActinsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntigens, CD20CYBB protein, humanMembrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesobinutuzumabReactive Oxygen SpeciesRNA, Small Interfering

Identifiers

PMID22354003
PMCPMC5944831
OpenAlexW2162335998

What OpenQuestion holds

Textmetadata
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.