Evidence map›Paper›PMID 25482129›Full record

ArticleLeukemia2015

PTPROt-mediated regulation of p53/Foxm1 suppresses leukemic phenotype in a CLL mouse model.

T Motiwala, H Kutay, N Zanesi, F W Frissora, X Mo, N Muthusamy, S T Jacob

Open access · bronzeAbstract read
In one paragraph

Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-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

10 citing papers in PubMed, 17 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

7 authors at 2 institutions in 1 country.

T MotiwalaDepartment of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, USA.
H KutayDepartment of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, USA.
N ZanesiDepartment of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, USA.
F W FrissoraComprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
X MoCenter for Biostatistics, The Ohio State University, Columbus, OH, USA.
N MuthusamyDepartment of Internal Medicine, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
S T Jacob1] Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, USA [2] Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
The Ohio State University · USThe Ohio State University Wexner Medical Center · US

Funding

PathologyP01CA101956 · NCI · OHIO STATE UNIVERSITY · PI BYRD, JOHN C. · 2006 to 2010
$11.4M
MOLECULAR MECHANISMS OF DIET-INDUCED CARCINOGENESISR01CA086978 · NCI · OHIO STATE UNIVERSITY · PI GHOSHAL, KALPANA, JACOB, SAMSON T · 2002 to 2018
$4.9M
The OSU Clinical and Translational Research Informatics Training Program (CTRIP)T15LM011270 · NLM · OHIO STATE UNIVERSITY · PI COOMBES, KEVIN ROBERT, JANIES, DANIEL A. · 2012 to 2016
$2.2M
NCI NIH HHS CA086978NCI NIH HHS CA101956NCI NIH HHS P01 CA101956NCI NIH HHS R01 CA086978NLM NIH HHS T15 LM011270
6 · The paper itself

Abstract

The gene encoding PTPROt (truncated isoform of protein tyrosine phosphatase receptor-type O) is methylated and suppressed in chronic lymphocytic leukemia (CLL). PTPROt exhibits in vitro tumor-suppressor characteristics through the regulation of B-cell receptor (BCR) signaling. Here we generated transgenic (Tg) mice with B-cell-specific expression of PTPROt. Although lymphocyte development is normal in these mice, crossing them with TCL1 Tg mouse model of CLL results in a survival advantage compared with the TCL1 Tg mice. Gene expression profiling of splenic B-lymphocytes before detectable signs of CLL followed by Ingenuity Pathway Analysis revealed that the most prominently regulated functions in TCL1 Tg vs non-transgenic (NTg) and TCL1 Tg vs PTPROt/TCL1 double Tg are the same and also biologically relevant to this study. Further, enhanced expression of the chemokine Ccl3, the oncogenic transcription factor Foxm1 and its targets in TCL1 Tg mice were significantly suppressed in the double Tg mice, suggesting a protective function of PTPROt against leukemogenesis. This study also showed that PTPROt-mediated regulation of Foxm1 involves activation of p53, a transcriptional repressor of Foxm1, which is facilitated through suppression of BCR signaling. These results establish the in vivo tumor-suppressive function of PTPROt and identify p53/Foxm1 axis as a key downstream effect of PTPROt-mediated suppression of BCR signaling.

Indexed as

Disease Models, AnimalAnimalsBiomarkers, TumorBlotting, WesternB-LymphocytesCells, CulturedFemaleFlow CytometryForkhead Box Protein M1Forkhead Transcription FactorsGene Expression ProfilingGene Expression Regulation, LeukemicHumansInflammationLeukemia, Lymphocytic, Chronic, B-CellMaleBcr protein, mouseBiomarkers, TumorForkhead Box Protein M1Forkhead Transcription FactorsFoxm1 protein, mouseProto-Oncogene ProteinsProto-Oncogene Proteins c-bcrPTPRO protein, humanReceptor-Like Protein Tyrosine Phosphatases, Class 3RNA, MessengerTCL1A protein, humanTumor Suppressor Protein p53

Identifiers

PMID25482129
PMCPMC4456291
OpenAlexW2081509524

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.