Evidence map›Paper›PMID 30223538›Full record

ArticleCancers2018

Clonal Heterogeneity Reflected by PI3K-AKT-mTOR Signaling in Human Acute Myeloid Leukemia Cells and Its Association with Adverse Prognosis.

Ina Nepstad, Kimberley Joanne Hatfield, Tor Henrik Anderson Tvedt, Håkon Reikvam, Øystein Bruserud

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

22 citing papers in PubMed, 43 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

5 authors at 2 institutions in 1 country.

Ina NepstadSection for Hematology, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway. ina.nepstad@uib.no.ORCID 0000-0002-9760-5131
Kimberley Joanne HatfieldSection for Hematology, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway. Kimberley.Hatfield@uib.no.
Tor Henrik Anderson TvedtSection for Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway. tor.henrik.anderson.tvedt@helse-bergen.no.
Håkon ReikvamSection for Hematology, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway. Hakon.Reikvam@uib.no.
Øystein BruserudSection for Hematology, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway. oystein.bruserud@helse-bergen.no.
Haukeland University Hospital · NOUniversity of Bergen · NO

Funding

Helse Vest 911788 and 912051Norwegian Cancer Society 100933, 17813, 62370, 62371, 145008, 15752 and 145007
6 · The paper itself

Abstract

Clonal heterogeneity detected by karyotyping is a biomarker associated with adverse prognosis in acute myeloid leukemia (AML). Constitutive activation of the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in AML cells, and this pathway integrates signaling from several upstream receptors/mediators. We suggest that this pathway reflects biologically important clonal heterogeneity. We investigated constitutive PI3K-Akt-mTOR pathway activation in primary human AML cells derived from 114 patients, together with 18 pathway mediators. The cohort included patients with normal karyotype or single karyotype abnormalities and with an expected heterogeneity of molecular genetic abnormalities. Clonal heterogeneity reflected as pathway mediator heterogeneity was detected for 49 patients. Global gene expression profiles of AML cell populations with and without clonal heterogeneity differed with regard to expression of ectopic olfactory receptors (a subset of G-protein coupled receptors) and proteins involved in G-protein coupled receptor signaling. Finally, the presence of clonal heterogeneity was associated with adverse prognosis for patients receiving intensive antileukemic treatment. The clonal heterogeneity as reflected in the activation status of selected mediators in the PI3K-Akt-mTOR pathway was associated with a different gene expression profile and had an independent prognostic impact. Biological heterogeneity reflected in the intracellular signaling status should be further investigated as a prognostic biomarker in human AML.

Indexed as

acute myeloid leukemiaAktclonal heterogeneitymTORphosphorylationPI3K

Identifiers

PMID30223538
PMCPMC6162751
OpenAlexW2890282014

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.