Evidence map›Paper›PMID 23892718›Full record

ArticleLeukemia2014

Targeting the PI3K/Akt/mTOR signaling pathway in B-precursor acute lymphoblastic leukemia and its therapeutic potential.

L M Neri, A Cani, A M Martelli, C Simioni, C Junghanss, G Tabellini, F Ricci, P L Tazzari, P Pagliaro, J A McCubrey and 1 more

Abstract read
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In one paragraph

Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 2 pooled it
12.4field-weighted citation impact, top 1% 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

78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 139 citations in OpenAlex.

  1. Pooled it
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  15. Combined BCL-2 and PI3K/AKT Pathway Inhibition inInternational journal of molecular sciences · 2023
    Article
  16. Article
  17. Article
  18. The Question of Survival or Death: What Is the Role of Autophagy in Acute Myeloid Leukemia (AML)?International journal of hematology-oncology and stem cell research · 2022
    Review
  19. Article
  20. Article

18 more citing papers are in PubMed but not listed here.

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 6 institutions in 3 countries.

L M NeriDepartment of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
A CaniDepartment of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
A M Martelli1] Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy [2] Institute of Molecular Genetics, National Research Council, Pavia, Italy.
C SimioniDepartment of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
C JunghanssUniversity of Rostock, Division of Medicine, Department of Hematology/Oncology/Palliative Medicine, Rostock, Germany.
G TabelliniDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
F RicciImmunohematology and Transfusion Center, Policlinico S.Orsola-Malpighi, Bologna, Italy.
P L TazzariImmunohematology and Transfusion Center, Policlinico S.Orsola-Malpighi, Bologna, Italy.
P PagliaroImmunohematology and Transfusion Center, Policlinico S.Orsola-Malpighi, Bologna, Italy.
J A McCubreyDepartment of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
S CapitaniDepartment of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
University of Ferrara · ITPoliclinico S.Orsola-Malpighi · ITEast Carolina University · USUniversity of Bologna · ITUniversity of Brescia · ITUniversity of Rostock · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

B-precursor acute lymphoblastic leukemia (B-pre ALL) is a malignant disorder characterized by the abnormal proliferation of B-cell progenitors. The prognosis of B-pre ALL has improved in pediatric patients, but the outcome is much less successful in adults. Constitutive activation of the phosphatidylinositol 3-kinase (PI3K), Akt and the mammalian target of rapamycin (mTOR) (PI3K/Akt/mTOR) network is a feature of B-pre ALL, where it strongly influences cell growth and survival. RAD001, a selective mTORC1 inhibitor, has been shown to be cytotoxic against many types of cancer including hematological malignancies. To investigate whether mTORC1 could represent a target in the therapy of B-pre ALL, we treated cell lines and adult patient primary cells with RAD001. We documented that RAD001 decreased cell viability, induced cell cycle arrest in G0/G1 phase and caused apoptosis in B-pre ALL cell lines. Autophagy was also induced, which was important for the RAD001 cytotoxic effect, as downregulation of Beclin-1 reduced drug cytotoxicity. RAD001 strongly synergized with the novel allosteric Akt inhibitor MK-2206 in both cell lines and patient samples. Similar results were obtained with the combination CCI-779 plus GSK 690693. These findings point out that mTORC1 inhibitors, either as a single agent or in combination with Akt inhibitors, could represent a potential therapeutic innovative strategy in B-pre ALL.

Indexed as

Phosphoinositide-3 Kinase InhibitorsApoptosisAutophagyCell Cycle CheckpointsCell Line, TumorCell ProliferationEverolimusHeterocyclic Compounds, 3-RingHumansMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesOxadiazolesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaProto-Oncogene Proteins c-aktSignal TransductionSirolimusEverolimusGSK690693Heterocyclic Compounds, 3-RingMechanistic Target of Rapamycin Complex 1MK 2206Multiprotein ComplexesOxadiazolesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktSirolimustemsirolimusTOR Serine-Threonine Kinases

Identifiers

PMID23892718
OpenAlexW2028744406

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.