Evidence map›Paper›PMID 25014496›Full record

ArticlePloS one2014

mTOR inhibition by everolimus in childhood acute lymphoblastic leukemia induces caspase-independent cell death.

Rana Baraz, Adam Cisterne, Philip O Saunders, John Hewson, Marilyn Thien, Jocelyn Weiss, Jordan Basnett, Kenneth F Bradstock, Linda J Bendall

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.0field-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

17 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
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  3. c-MYC-mediated TRIB3/P62Acta pharmaceutica Sinica. B · 2022
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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

9 authors at 3 institutions in 1 country.

Rana BarazCentre for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
Adam CisterneCentre for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
Philip O SaundersCentre for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
John HewsonCentre for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
Marilyn ThienCentre for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
Jocelyn WeissCentre for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
Jordan BasnettCentre for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
Kenneth F BradstockDepartment of Haematology, Westmead Hospital, Westmead, NSW, Australia.
Linda J BendallCentre for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
The University of Sydney · AUWestmead Institute · AUWestmead Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Increasingly, anti-cancer medications are being reported to induce cell death mechanisms other than apoptosis. Activating alternate death mechanisms introduces the potential to kill cells that have defects in their apoptotic machinery, as is commonly observed in cancer cells, including in hematological malignancies. We, and others, have previously reported that the mTOR inhibitor everolimus has pre-clinical efficacy and induces caspase-independent cell death in acute lymphoblastic leukemia cells. Furthermore, everolimus is currently in clinical trial for acute lymphoblastic leukemia. Here we characterize the death mechanism activated by everolimus in acute lymphoblastic leukemia cells. We find that cell death is caspase-independent and lacks the morphology associated with apoptosis. Although mitochondrial depolarization is an early event, permeabilization of the outer mitochondrial membrane only occurs after cell death has occurred. While morphological and biochemical evidence shows that autophagy is clearly present it is not responsible for the observed cell death. There are a number of features consistent with paraptosis including morphology, caspase-independence, and the requirement for new protein synthesis. However in contrast to some reports of paraptosis, the activation of JNK signaling was not required for everolimus-induced cell death. Overall in acute lymphoblastic leukemia cells everolimus induces a cell death that resembles paraptosis.

Indexed as

Gene Expression Regulation, NeoplasticAntineoplastic AgentsCaspasesCell DeathCell Line, TumorChildDose-Response Relationship, DrugEndoplasmic Reticulum StressEverolimusHumansMitochondriaMitochondrial MembranesPrecursor Cell Lymphoblastic Leukemia-LymphomaSignal TransductionSirolimusTOR Serine-Threonine KinasesAntineoplastic AgentsCaspasesEverolimusMTOR protein, humanSirolimusTOR Serine-Threonine Kinases

Identifiers

PMID25014496
PMCPMC4094511
OpenAlexW2049065975

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.