Evidence map›Paper›PMID 26997274›Full record

ArticleCell reports2016

NPM and BRG1 Mediate Transcriptional Resistance to Retinoic Acid in Acute Promyelocytic Leukemia.

Jessica N Nichol, Matthew D Galbraith, Claudia L Kleinman, Joaquín M Espinosa, Wilson H Miller

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

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

7 citing papers in PubMed, 16 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 4 institutions in 2 countries.

Jessica N NicholDivision of Experimental Medicine, Department of Oncology, Segal Cancer Centre and Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC H3T 1E2, Canada.
Matthew D GalbraithDepartment of Pharmacology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Molecular, Cellular, and Developmental Biology and Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO 80309, USA.
Claudia L KleinmanDepartment of Human Genetics, Segal Cancer Centre and Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC H3T 1E2, Canada.
Joaquín M EspinosaDepartment of Pharmacology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Molecular, Cellular, and Developmental Biology and Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO 80309, USA; Linda Crnic Institute for Down Syndrome, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Wilson H MillerDivision of Experimental Medicine, Department of Oncology, Segal Cancer Centre and Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC H3T 1E2, Canada. Electronic address: wmiller@ldi.jgh.mcgill.ca.
McGill University · CAHoward Hughes Medical Institute · USJewish General Hospital · CAUniversity of Colorado Boulder · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Stress- and Promoter-Specific Mechanisms of Transcritpional Activation by p53R01CA117907 · NCI · UNIVERSITY OF COLORADO DENVER · PI ESPINOSA, JOAQUIN M. · 2006 to 2022
$4.4M
Canadian Institutes of Health Research MOP-12863NCI NIH HHS 2R01CA117907-08NCI NIH HHS 5P30CA046934-27NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA117907
6 · The paper itself

Abstract

Perturbation in the transcriptional control of genes driving differentiation is an established paradigm whereby oncogenic fusion proteins promote leukemia. From a retinoic acid (RA)-sensitive acute promyelocytic leukemia (APL) cell line, we derived an RA-resistant clone characterized by a block in transcription initiation, despite maintaining wild-type PML/RARA expression. We uncovered an aberrant interaction among PML/RARA, nucleophosmin (NPM), and topoisomerase II beta (TOP2B). Surprisingly, RA stimulation in these cells results in enhanced chromatin association of the nucleosome remodeler BRG1. Inhibition of NPM or TOP2B abrogated BRG1 recruitment. Furthermore, NPM inhibition and targeting BRG1 restored differentiation when combined with RA. Here, we demonstrate a role for NPM and BRG1 in obstructing RA differentiation and implicate chromatin remodeling in mediating therapeutic resistance in malignancies. NPM mutations are the most common genetic change in patients with acute leukemia (AML); therefore, our model may be applicable to other more common leukemias driven by NPM.

Indexed as

CCAAT-Enhancer-Binding Protein-betaCell DifferentiationCell Line, TumorChromatin Assembly and DisassemblyChromatin ImmunoprecipitationDNA-Binding ProteinsDNA HelicasesDNA Topoisomerases, Type IIDrug Resistance, NeoplasmHumansLeukemia, Promyelocytic, AcuteNuclear ProteinsNucleophosminPoly-ADP-Ribose Binding ProteinsPromoter Regions, GeneticPromyelocytic Leukemia ProteinCCAAT-Enhancer-Binding Protein-betaCEBPB protein, humanDNA-Binding ProteinsDNA HelicasesDNA Topoisomerases, Type IINPM1 protein, humanNuclear ProteinsNucleophosminPML protein, humanPoly-ADP-Ribose Binding ProteinsPromyelocytic Leukemia ProteinRARA protein, humanRetinoic Acid Receptor alphaRNA, Small InterferingSMARCA4 protein, humanTOP2B protein, humanTranscription FactorsTretinoin

Identifiers

PMID26997274
PMCPMC4814328
OpenAlexW2299942500

What OpenQuestion holds

Textmetadata
LicenceTDM
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.