Evidence map›Paper›PMID 24439051›Full record

ArticleLeukemia research2014

Poly(ADP-ribose) polymerase inhibitor CEP-8983 synergizes with bendamustine in chronic lymphocytic leukemia cells in vitro.

Robert L Dilley, Weijie Poh, Douglas E Gladstone, James G Herman, Margaret M Showel, Judith E Karp, Michael A McDevitt, Keith W Pratz

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

Article in Leukemia research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.1field-weighted citation impact, top 46% 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

3 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Review
  3. 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 1 institution in 1 country.

Robert L DilleyDepartment of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Weijie PohDepartment of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Douglas E GladstoneDepartment of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
James G HermanDepartment of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Margaret M ShowelDepartment of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Judith E KarpDepartment of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Michael A McDevittDepartment of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Keith W PratzDepartment of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA. Electronic address: kpratz1@jhmi.edu.
Johns Hopkins University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
NCATS NIH HHS UL1 TR001079NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

DNA repair aberrations and associated chromosomal instability is a feature of chronic lymphocytic leukemia (CLL). To evaluate if DNA repair insufficiencies are related to methylation changes, we examined the methylation of nine promoter regions of DNA repair proteins by bisulfide sequencing in 26 CLL primary samples and performed quantitative PCR on a subset of samples to examine BRCA1 expression. We also investigated if changes in cytogenetic or expression level of DNA repair proteins led to changes in sensitivity to a novel PARP inhibitor, CEP-8983, alone and in combination with bendamustine. No changes in promoter methylation were identified in BRCA1, BRCA2, FANC-C, FANC-F, FANC-L, ATM, MGMT, hMLH1 and H2AX except for two cases of minor BRCA1 hypermethylation. CLL samples appeared to have reduced BRCA1 mRNA expression uniformly in comparison to non-malignant lymphocytes irrespective of promoter hypermethylation. CEP-8983 displayed single agent cytotoxicity and the combination with bendamustine demonstrated synergistic cytotoxicity in the majority of CLL samples. These results were consistent across cytogenetic subgroups, including 17p deleted and previously treated patients. Our results provide rationale for further exploration of the combination of a PARP inhibitor and DNA damaging agents as a novel therapeutic strategy in CLL.

Indexed as

Poly(ADP-ribose) Polymerase InhibitorsAntineoplastic Agents, AlkylatingBendamustine HydrochlorideB-LymphocytesBRCA1 ProteinCarbazolesDNA DamageDNA MethylationDNA, NeoplasmDNA RepairDNA Repair EnzymesDrug SynergismEnzyme InhibitorsGene Expression Regulation, LeukemicHumansLeukemia, Lymphocytic, Chronic, B-CellAntineoplastic Agents, AlkylatingBendamustine HydrochlorideBRCA1 ProteinBRCA1 protein, humanCarbazolesCEP 8983DNA, NeoplasmDNA Repair EnzymesEnzyme InhibitorsNitrogen Mustard CompoundsPhthalimidesPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesBendamustineCEP-8983Chronic lymphocytic leukemia (CLL)Poly(ADP-ribose) polymerase (PARP)

Identifiers

PMID24439051
PMCPMC4142574
OpenAlexW2061448684

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.