Evidence map›Paper›PMID 24473562›Full record

ArticleClinics (Sao Paulo, Brazil)2014

Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cells.

Veronica Tisato, Alessia Norcio, Claudio Celeghini, Daniela Milani, Arianna Gonelli, Paola Secchiero

Abstract read
In one paragraph

Article in Clinics (Sao Paulo, Brazil), 2014. 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
–field-weighted citation impact
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.

  1. Article
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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

6 authors.

Veronica TisatoSurgery and Experimental Medicine and LTTA Centre, Department of Morphology, University of Ferrara, Ferrara, Italy, University of Ferrara, Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, Ferrara, Italy.
Alessia NorcioIRCCS "Burlo Garofolo", Institute for Maternal and Child Health, Trieste, Italy, Institute for Maternal and Child Health, IRCCS ''Burlo Garofolo'', Trieste, Italy.
Claudio CeleghiniDepartment of Life Sciences, University of Trieste, Trieste, Italy, University of Trieste, Department of Life Sciences, Trieste, Italy.
Daniela MilaniSurgery and Experimental Medicine and LTTA Centre, Department of Morphology, University of Ferrara, Ferrara, Italy, University of Ferrara, Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, Ferrara, Italy.
Arianna GonelliSurgery and Experimental Medicine and LTTA Centre, Department of Morphology, University of Ferrara, Ferrara, Italy, University of Ferrara, Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, Ferrara, Italy.
Paola SecchieroSurgery and Experimental Medicine and LTTA Centre, Department of Morphology, University of Ferrara, Ferrara, Italy, University of Ferrara, Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, Ferrara, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveIt has been shown that SOCS-1 plays an important role in the proper control of cytokine/growth factor responses and acts as a tumor suppressor in acute myeloid leukemias. Therefore, the objective of the present study was to evaluate the in vitro effect of treatment with Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, on the expression of the suppressor of cytokine signaling 1 in primary acute myeloid leukemia cells and in myeloid cell lines with differential p53 status.

methodThe expression of the suppressor of cytokine signaling 1 was quantitatively analyzed by real-time PCR in myeloid p53wild-type (OCI and MOLM) and p53null HL-60, leukemic cell lines, in patient-derived acute myeloid leukemia blasts, and in primary normal cell types, such as macrophages, endothelial cells, and bone marrow mesenchymal stem cells. The p53-dependence of the suppressor of cytokine signaling 1 upregulation that is induced by Nutlin-3 was analyzed in experiments performed using siRNA for p53, while the functional upregulation of the suppressor of cytokine signaling 1 was analyzed by assessing the levels of phosphorylated STAT-3.

resultsNutlin-3 significantly upregulated the transcription of the suppressor of cytokine signaling 1 in p53wild-type OCI and MOLM but not in p53deleted p53null HL60, myeloid leukemic cell lines, as well as in primary acute myeloid leukemia blasts. Conversely, and somewhat unexpectedly, Nutlin-3 did not modulate the suppressor of cytokine signaling 1 expression in primary normal macrophages, endothelial cells, and bone marrow mesenchymal stem cells. The p53-dependent upregulation of the suppressor of cytokine signaling 1 by Nutlin-3 was associated with the downregulation of phosphorylated STAT-3, a major molecular target of the suppressor of cytokine signaling 1.

conclusionOverall, our data suggest a potential role for the suppressor of cytokine signaling 1 as a therapeutic target of Nutlin-3 in p53 wild-type acute myeloid leukemias.

Indexed as

Blotting, WesternCell Line, TumorCells, CulturedCell SurvivalEndothelial CellsHumansImidazolesLeukemia, Myeloid, AcuteMyeloid CellsPiperazinesReal-Time Polymerase Chain ReactionReproducibility of ResultsSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling ProteinsTime FactorsTumor Suppressor Protein p53Imidazolesnutlin 3PiperazinesSOCS1 protein, humanSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling ProteinsTumor Suppressor Protein p53

Identifiers

PMID24473562
PMCPMC3870313

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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.