Evidence map›Paper›PMID 20200558›Full record

ArticleLeukemia2010

Targeting PKC delta-mediated topoisomerase II beta overexpression subverts the differentiation block in a retinoic acid-resistant APL cell line.

S McNamara, J N Nichol, H Wang, W H Miller

Abstract read
PubMed Publisher
In one paragraph

Article in Leukemia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.3field-weighted citation impact, top 41% 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

11 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. TOP2B: The First Thirty Years.International journal of molecular sciences · 2018
    Review
  7. The Roles of DNA Topoisomerase IIβ in Transcription.International journal of molecular sciences · 2018
    Review
  8. Article
  9. Article
  10. Article
  11. Article
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

4 authors at 2 institutions in 1 country.

S McNamaraDivision of Experimental Medicine, Department of Oncology, Segal Cancer Comprehensive Centre, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
J N Nichol
H Wang
W H Miller
Jewish General Hospital · CAMcGill University · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Retinoic acid (RA) relieves the maturation block in t(15:17) acute promyelocytic leukemia (APL), leading to granulocytic differentiation. However, RA treatment alone invariably results in RA resistance, both in vivo and in vitro. RA-resistant cell lines have been shown to serve as useful models for elucidation of mechanisms of resistance. Previously, we identified topoisomerase II beta (TOP2B) as a novel mediator of RA-resistance in APL cell lines. In this study, we show that both TOP2B protein stability and activity are regulated by a member of the protein kinase C (PRKC) family, PRKC delta (PRKCD). Co-treatment with a pharmacologic inhibitor of PRKCD and RA resulted in the induction of an RA responsive reporter construct, as well as the endogenous RA target genes, CEBPE, CYP26A1 and RIG-I. Furthermore, the co-treatment overcame the differentiation block in RA-resistant cells, as assessed by morphological analysis, restoration of promyelocytic leukemia nuclear bodies, induction of CD11c cell surface expression and an increase in nitro-blue-tetrazolium reduction. Cumulatively, our data suggest a model whereby inhibition of PRKCD decreases TOP2B protein levels, leading to a loss of TOP2B-mediated repressive effects on RA-induced transcription and granulocytic differentiation.

Indexed as

Drug Resistance, NeoplasmAntineoplastic AgentsBlotting, WesternCell DifferentiationCell Line, TumorDNA-Binding ProteinsDNA Topoisomerases, Type IIFluorescent Antibody TechniqueGene Expression Regulation, LeukemicHumansLeukemia, Promyelocytic, AcutePhosphorylationPoly-ADP-Ribose Binding ProteinsProtein Kinase C-deltaReverse Transcriptase Polymerase Chain ReactionRNA, MessengerAntineoplastic AgentsDNA-Binding ProteinsDNA Topoisomerases, Type IIPoly-ADP-Ribose Binding ProteinsProtein Kinase C-deltaRNA, MessengerTOP2B protein, humanTretinoin

Identifiers

PMID20200558
OpenAlexW2038778317

What OpenQuestion holds

Textmetadata
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.