Evidence map›Paper›PMID 27655686›Full record

ArticleOncotarget2016

Targeting p53-deficient chronic lymphocytic leukemia cells in vitro and in vivo by ROS-mediated mechanism.

Jinyun Liu, Gang Chen, Helene Pelicano, Jianwei Liao, Jie Huang, Li Feng, Michael J Keating, Peng Huang

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
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  6. Article
  7. Review
  8. Gain of Function (GOF) Mutant p53 in Cancer-Current Therapeutic Approaches.International journal of molecular sciences · 2022
    Review
  9. Review
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  11. Review
  12. Article
  13. Review
  14. Review
  15. Role of Phytochemicals in Cancer Prevention.International journal of molecular sciences · 2019
    Review
  16. 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

8 authors at 2 institutions in 2 countries.

Jinyun LiuDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Gang ChenDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Helene PelicanoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Jianwei LiaoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Jie HuangDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Li FengDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Michael J KeatingDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Peng HuangDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
The University of Texas MD Anderson Cancer Center · USSun Yat-sen University · CN

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Superoxide, ROS, and novel targets for cancer therapyR01CA085563 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HUANG, PENG · 2001 to 2016
$3.1M
Novel Strategies to Target Leukemia-Stromal InteractionsR01CA172724 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI PELICANO, HELENE · 2015 to 2019
$1.8M
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA085563NCI NIH HHS R01 CA172724
6 · The paper itself

Abstract

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Loss of p53 function in CLL cells due to chromosome 17p deletion or p53 mutations often leads to a more malignant disease phenotype and is associated with drug resistance and poor clinical outcome. Thus, development of novel therapeutic strategies to effectively target CLL cells with p53 deficiency is clinically important. Here we showed that p53-null CLL cells were highly sensitive to ROS-mediated cell killing due to their intrinsic ROS stress. We further demonstrated that a natural compound phenethyl isothiocyanate (PEITC) was able to effectively kill CLL cells with loss of p53, even under the protection of stromal cells. In p53-defficient CLL cells, PEITC induced a rapid depletion of glutathione and a severe accumulation of ROS, leading to massive leukemia cell death in the stromal microenvironment. The drug-induced cell death was associated with a significant decrease of in MCL-1 survival molecule. We further showed that ROS-mediated cell death was the key mechanism by which PEITC induced cytotoxicity, since such cell death could be prevented by addition of antioxidant NAC. Importantly, in vivo study showed that PEITC was able to induce substantial leukemia cell death in mice. Treatment of CLL mice harboring TCL1-Tg:p53-/- genotype with PEITC significantly prolonged the median survival time of the animals. Our study identifies a vulnerability of p53-null CLL cells with high sensitivity to ROS-generating agents, and suggests that PEITC may potentially be useful for clinical treatment of CLL with 17p deletion and p53 mutations.

Indexed as

MutationAnimalsChromosome DeletionChromosomes, Human, Pair 17GlutathioneHumansIsothiocyanatesLeukemia, Lymphocytic, Chronic, B-CellMiceMyeloid Cell Leukemia Sequence 1 ProteinReactive Oxygen SpeciesTumor Suppressor Protein p53GlutathioneIsothiocyanatesMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 Proteinphenethyl isothiocyanateReactive Oxygen SpeciesTumor Suppressor Protein p53CLLoxidative stressp53PEITC

Identifiers

PMID27655686
PMCPMC5342085
OpenAlexW2548097153

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.