Evidence map›Paper›PMID 25944917›Full record

ArticleMolecular cancer research : MCR2015

EphB1 Suppression in Acute Myelogenous Leukemia: Regulating the DNA Damage Control System.

K R Kampen, F J G Scherpen, G Garcia-Manero, H Yang, G J L Kaspers, J Cloos, C M Zwaan, M M van den Heuvel-Eibrink, S M Kornblau, E S J M De Bont

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cancer research : MCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-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

13 citing papers in PubMed, 21 citations in OpenAlex.

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  13. Prognostic values of EphB1/B2 and p-EphB1/B2 expression in non-small cell lung cancer.International journal of clinical and experimental pathology · 2017
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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

10 authors at 4 institutions in 2 countries.

K R KampenDepartment of Pediatric Oncology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
F J G ScherpenDepartment of Pediatric Oncology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
G Garcia-ManeroDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
H YangDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
G J L KaspersDepartment of Pediatric Oncology, VU University Medical Center, Amsterdam, the Netherlands.
J CloosDepartment of Pediatric Oncology, VU University Medical Center, Amsterdam, the Netherlands.
C M ZwaanDepartment of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
M M van den Heuvel-EibrinkDepartment of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
S M KornblauDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
E S J M De BontDepartment of Pediatric Oncology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. e.s.j.m.de.bont@umcg.nl.
The University of Texas MD Anderson Cancer Center · USUniversity Medical Center Groningen · NLAmsterdam UMC Location Vrije Universiteit Amsterdam · NLErasmus MC - Sophia Children’s Hospital · NL

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

unlabelledLoss of ephrin receptor (EphB1) expression may associate with aggressive cancer phenotypes; however, the mechanism of action remains unclear. To gain detailed insight into EphB1 function in acute myelogenous leukemia (AML), comprehensive analysis of EphB1 transcriptional regulation was conducted. In AML cells, EphB1 transcript was inversely correlated with EphB1 promoter methylation. The presence of EphB1 allowed EfnB1 ligand-mediated p53 DNA binding, leading to restoration of the DNA damage response (DDR) cascade by the activation of ATR, Chk1, p53, p21, p38, CDK1(tyr15), and Bax, and downregulation of HSP27 and Bcl2. Comparatively, reintroduction of EphB1 expression in EphB1-methylated AML cells enhanced the same cascade of ATR, Chk1, p21, and CDK1(tyr15), which consequently enforced programmed cell death. Interestingly, in pediatric AML samples, EphB1 peptide phosphorylation and mRNA expression were actively suppressed as compared with normal bone marrow, and a significant percentage of the primary AML specimens had EphB1 promoter hypermethylation. Finally, EphB1 repression associated with a poor overall survival in pediatric AML. Combined, the contribution of EphB1 to the DDR system reveals a tumor-suppressor function for EphB1 in pediatric AML. IMPLICATIONS: The tumor-suppressor function of EphB1 is clinically relevant across many malignancies, suggesting that EphB1 is an important regulator of common cancer cell transforming pathways.

Indexed as

DNA DamageDown-RegulationApoptosisBone MarrowCell Line, TumorChildDNA MethylationDNA RepairG2 Phase Cell Cycle CheckpointsHumansLeukemia, Myeloid, AcutePromoter Regions, GeneticReceptor, EphA1Receptor, EphB2EPHB2 protein, humanReceptor, EphA1Receptor, EphB2

Identifiers

PMID25944917
PMCPMC4983719
OpenAlexW1943211412

What OpenQuestion holds

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Registered trials

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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.