Evidence map›Paper›PMID 36224199›Full record

ArticleNature communications2022

Differential ABC transporter expression during hematopoiesis contributes to neutrophil-biased toxicity of Aurora kinase inhibitors.

David B Chou, Brooke A Furlong, Ryan R Posey, Christos Kyprianou, Lucy R O'Sullivan, Rhiannon David, Suzanne J Randle, Urszula M Polanska, Jon Travers, Jelena Urosevic and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 36% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Human organ chips for regenerative pharmacology.Pharmacology research & perspectives · 2024
    Review
  3. ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024
    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

16 authors at 4 institutions in 2 countries.

David B Chou *Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.ORCID 0000-0002-1659-9308
Brooke A Furlong *Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.ORCID 0000-0001-7584-0707
Ryan R Posey *Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
Christos KyprianouWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.ORCID 0000-0001-8516-9195
Lucy R O'SullivanWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
Rhiannon DavidSafety Sciences, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK.
Suzanne J RandleSafety Sciences, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK.
Urszula M PolanskaEarly Oncology, R&D, AstraZeneca, Cambridge, UK.
Jon TraversEarly Oncology, R&D, AstraZeneca, Cambridge, UK.
Jelena UrosevicEarly Oncology, R&D, AstraZeneca, Cambridge, UK.
John N HutchinsonHarvard Chan Bioinformatics Core, Boston, MA, USA.
Jianwei CheDepartment of Cancer Biology, Dana-Farber Cancer Institute, and Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Anna M HowleyWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
Robert P HasserjianDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Rachelle Prantil-BaunWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
Donald E IngberWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.ORCID 0000-0002-4319-6520
Harvard University · USAstraZeneca (United Kingdom) · GBBoston Children's Hospital · USMassachusetts General Hospital · US

Funding

MOLECULAR IMMUNOLOGY AND TUMOR BIOLOGYT32CA009216 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Michael Langenau · 1985 to 2026
$10.6M
FDA HHS HHSF223201310079CNCI NIH HHS T32 CA009216
6 · The paper itself

Abstract

Drug-induced cytopenias are a prevalent and significant issue that worsens clinical outcomes and hinders the effective treatment of cancer. While reductions in blood cell numbers are classically associated with traditional cytotoxic chemotherapies, they also occur with newer targeted small molecules and the factors that determine the hematotoxicity profiles of oncologic drugs are not fully understood. Here, we explore why some Aurora kinase inhibitors cause preferential neutropenia. By studying drug responses of healthy human hematopoietic cells in vitro and analyzing existing gene expression datasets, we provide evidence that the enhanced vulnerability of neutrophil-lineage cells to Aurora kinase inhibition is caused by early developmental changes in ATP-binding cassette (ABC) transporter expression. These data show that hematopoietic cell-intrinsic expression of ABC transporters may be an important factor that determines how some Aurora kinase inhibitors affect the bone marrow.

Indexed as

ATP-Binding Cassette TransportersNeutrophilsAdenosine TriphosphateATP Binding Cassette Transporter, Subfamily G, Member 2Aurora KinasesHematopoiesisHumansNeoplasm ProteinsProtein Kinase InhibitorsAdenosine TriphosphateATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2Aurora KinasesNeoplasm ProteinsProtein Kinase Inhibitors

Identifiers

PMID36224199
PMCPMC9556712
OpenAlexW4304698184

What OpenQuestion holds

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LicenceCC BY
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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.