Evidence map›Paper›PMID 31240133›Full record

ArticleSignal transduction and targeted therapy

Effects of insulin and pathway inhibitors on the PI3K-Akt-mTOR phosphorylation profile in acute myeloid leukemia cells.

Ina Nepstad, Kimberley Joanne Hatfield, Ida Sofie Grønningsæter, Elise Aasebø, Maria Hernandez-Valladares, Karen Marie Hagen, Kristin Paulsen Rye, Frode S Berven, Frode Selheim, Håkon Reikvam and 1 more

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

Article in Signal transduction and targeted therapy. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

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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

11 authors at 2 institutions in 1 country.

Ina Nepstad1Section for Hematology, Department of Clinical Science, University of Bergen, Bergen, Norway.
Kimberley Joanne Hatfield1Section for Hematology, Department of Clinical Science, University of Bergen, Bergen, Norway.
Ida Sofie Grønningsæter1Section for Hematology, Department of Clinical Science, University of Bergen, Bergen, Norway.
Elise Aasebø1Section for Hematology, Department of Clinical Science, University of Bergen, Bergen, Norway.
Maria Hernandez-Valladares1Section for Hematology, Department of Clinical Science, University of Bergen, Bergen, Norway.
Karen Marie Hagen1Section for Hematology, Department of Clinical Science, University of Bergen, Bergen, Norway.
Kristin Paulsen Rye1Section for Hematology, Department of Clinical Science, University of Bergen, Bergen, Norway.
Frode S Berven3Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.
Frode Selheim3Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.
Håkon Reikvam1Section for Hematology, Department of Clinical Science, University of Bergen, Bergen, Norway.
Øystein Bruserud1Section for Hematology, Department of Clinical Science, University of Bergen, Bergen, Norway.
University of Bergen · NOHaukeland University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The phosphatidylinositol 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) pathway is constitutively activated in human acute myeloid leukemia (AML) cells and is regarded as a possible therapeutic target. Insulin is an agonist of this pathway and a growth factor for AML cells. We characterized the effect of insulin on the phosphorylation of 10 mediators in the main track of the PI3K-Akt-mTOR pathway in AML cells from 76 consecutive patients. The overall results showed that insulin significantly increased the phosphorylation of all investigated mediators. However, insulin effects on the pathway activation profile varied among patients, and increased phosphorylation in all mediators was observed only in a minority of patients; in other patients, insulin had divergent effects. Global gene expression profiling and proteomic/phosphoproteomic comparisons suggested that AML cells from these two patient subsets differed with regard to AML cell differentiation, transcriptional regulation, RNA metabolism, and cellular metabolism. Strong insulin-induced phosphorylation was associated with weakened antiproliferative effects of metabolic inhibitors. PI3K, Akt, and mTOR inhibitors also caused divergent effects on the overall pathway phosphorylation profile in the presence of insulin, although PI3K and Akt inhibition caused a general reduction in Akt pT308 and 4EBP1 pT36/pT45 phosphorylation. For Akt inhibition, the phosphorylation of upstream mediators was generally increased or unaltered. In contrast, mTOR inhibition reduced mTOR pS2448 and S6 pS244 phosphorylation but increased Akt pT308 phosphorylation. In conclusion, the effects of both insulin and PI3K-Akt-mTOR inhibitors differ between AML patient subsets, and differences in insulin responsiveness are associated with differential susceptibility to metabolic targeting.

Indexed as

Gene expression analysisHaematological cancerMolecular biologyMolecular medicine

Identifiers

PMID31240133
PMCPMC6582141
OpenAlexW2949891573

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.