Evidence map›Paper›PMID 26434776›Full record

ArticleAnalytical chemistry2015

Triomics Analysis of Imatinib-Treated Myeloma Cells Connects Kinase Inhibition to RNA Processing and Decreased Lipid Biosynthesis.

Susanne B Breitkopf, Min Yuan, Katja P Helenius, Costas A Lyssiotis, John M Asara

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Analytical chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05539079 (A Prospective Long-term Observational Study in Patients With Monoclonal Gammopathy of Undetermined Significance), which is not on this map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.4field-weighted citation impact, top 7% 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.

NCT05539079 recruitingnot on this mapstarted 2023, after this paper: background citation

A Prospective Long-term Observational Study in Patients With Monoclonal Gammopathy of Undetermined Significance

TypeobservationalSponsorOxford University Hospitals NHS TrustRan2023 to 2032Enrolled2,000ConditionsMGUS
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 28 citations in OpenAlex.

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  9. Tyrosine Kinase Inhibitors Increase MCL1 Degradation and in Combination with BCLXL/BCL2 Inhibitors Drive Prostate Cancer Apoptosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018
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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 4 institutions in 1 country.

Susanne B BreitkopfDivision of Signal Transduction, Beth Israel Deaconess Medical Center , Boston, Massachusetts 02115, United States.
Min YuanDivision of Signal Transduction, Beth Israel Deaconess Medical Center , Boston, Massachusetts 02115, United States.
Katja P HeleniusDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Costas A LyssiotisDepartment of Molecular and Integrative Physiology and Division of Gastroenterology, Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan 48109, United States.
John M AsaraDivision of Signal Transduction, Beth Israel Deaconess Medical Center , Boston, Massachusetts 02115, United States.
Beth Israel Deaconess Medical Center · USHarvard University · USMassachusetts Institute of Technology · USUniversity of Michigan–Ann Arbor · US

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9M
High Resolution Mass Spectrometry SystemS10OD010612 · OD · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ASARA, JOHN M · 2012 to 2012
$600k
NCI NIH HHS 5P01CA120964NCI NIH HHS 5P30CA006516NCI NIH HHS P01 CA120964NCI NIH HHS P30 CA006516NIH HHS 1S10OD010612NIH HHS S10 OD010612
6 · The paper itself

Abstract

The combination of metabolomics, lipidomics, and phosphoproteomics that incorporates triple stable isotope labeling by amino acids in cell culture (SILAC) protein labeling, as well as (13)C in vivo metabolite labeling, was demonstrated on BCR-ABL-positive H929 multiple myeloma cells. From 11 880 phosphorylation sites, we confirm that H929 cells are primarily signaling through the BCR-ABL-ERK pathway, and we show that imatinib treatment not only downregulates phosphosites in this pathway but also upregulates phosphosites on proteins involved in RNA expression. Metabolomics analyses reveal that BCR-ABL-ERK signaling in H929 cells drives the pentose phosphate pathway (PPP) and RNA biosynthesis, where pathway inhibition via imatinib results in marked PPP impairment and an accumulation of RNA nucleotides and negative regulation of mRNA. Lipidomics data also show an overall reduction in lipid biosynthesis and fatty acid incorporation with a significant decrease in lysophospholipids. RNA immunoprecipitation studies confirm that RNA degradation is inhibited with short imatinib treatment and transcription is inhibited upon long imatinib treatment, validating the triomics results. These data show the utility of combining mass spectrometry-based "-omics" technologies and reveals that kinase inhibitors may not only downregulate phosphorylation of their targets but also induce metabolic events via increased phosphorylation of other cellular components.

Indexed as

Antineoplastic AgentsCell Line, TumorHumansImatinib MesylateLipidsMultiple MyelomaRNA Processing, Post-TranscriptionalAntineoplastic AgentsImatinib MesylateLipids

Identifiers

PMID26434776
PMCPMC5585869
OpenAlexW2291477018

What OpenQuestion holds

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Registered trials

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.