Evidence map›Paper›PMID 28682312›Full record

ArticleCell death & disease2017

The BH3-only proteins BIM and PUMA are not critical for the reticulocyte apoptosis caused by loss of the pro-survival protein BCL-XL.

Alex Rd Delbridge, Brandon J Aubrey, Craig Hyland, Jonathan P Bernardini, Ladina Di Rago, Jean-Marc Garnier, Guillaume Lessene, Andreas Strasser, Warren S Alexander, Stephanie Grabow

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 20 citations in OpenAlex.

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  15. Manipulating Eryptosis of Human Red Blood Cells: A Novel Antimalarial Strategy?Frontiers in cellular and infection microbiology · 2018
    Review
  16. Anti-apoptotic BCL-2 family members in development.Cell death and differentiation · 2018
    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

10 authors at 2 institutions in 1 country.

Alex Rd DelbridgeThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Brandon J AubreyThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Craig HylandThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Jonathan P BernardiniThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Ladina Di RagoThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Jean-Marc GarnierThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Guillaume LesseneThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.ORCID 0000-0002-1193-8147
Andreas StrasserThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Warren S AlexanderThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Stephanie GrabowThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.ORCID 0000-0003-0467-7871
The University of Melbourne · AUWalter and Eliza Hall Institute of Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anaemia is a major global health problem arising from diverse causes and for which improved therapeutic strategies are needed. Erythroid cells can undergo apoptotic cell death and loss of pro-survival BCL-XL is known to trigger apoptosis during late-stage erythroid development. However, the mechanism by which loss or pharmacological blockade of BCL-XL leads to erythroid cell apoptosis remains unclear. Here we sought to identify the precise stage of erythropoiesis that depends on BCL-XL. We also tested whether deficiency of BIM or PUMA, the two main pro-apoptotic antagonists of BCL-XL, could prevent reticulocyte death and anaemia caused by BCL-XL loss. Using an in vivo mouse model of tamoxifen-inducible Bclx gene deletion and in vitro assays with a BCL-XL-selective inhibitor, we interrogated each stage of erythrocyte differentiation for BCL-XL dependency. This revealed that reticulocytes, but not orthochromatic erythroblasts, require BCL-XL for their survival. Surprisingly, concurrent loss of BIM or PUMA had no significant impact on the development of anemia following acute BCL-XL deletion in vivo. However, analysis of mixed bone marrow chimaeric mice revealed that loss of PUMA, but not loss of BIM, partially alleviated impaired erythropoiesis caused by BCL-XL deficiency. Insight into how the network of pro-survival and pro-apoptotic proteins works will assist the development of strategies to mitigate the effects of abnormal cell death during erythropoiesis and prevent anaemia in patients treated with BCL-XL-specific BH3-mimetic drugs.

Indexed as

Gene Expression RegulationAnemiaAnimalsApoptosisApoptosis Regulatory ProteinsBcl-2-Like Protein 11bcl-X ProteinBenzothiazolesCell SurvivalDisease Models, AnimalErythroblastsErythropoiesisGene DeletionHumansIsoquinolinesMiceA-1331852Apoptosis Regulatory ProteinsBcl2l11 protein, mouseBCL2L1 protein, humanBcl-2-Like Protein 11bcl-X ProteinBenzothiazolesIsoquinolinesPUMA protein, mouseTamoxifenTumor Suppressor Proteins

Identifiers

PMID28682312
PMCPMC5550852
OpenAlexW2731426746

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.