Evidence map›Paper›PMID 27052408›Full record

ArticleJournal of hematology & oncology2016

PML-RAR alpha induces the downmodulation of HHEX: a key event responsible for the induction of an angiogenetic response.

Ernestina Saulle, Alessia Petronelli, Elvira Pelosi, Elena Coppotelli, Luca Pasquini, Ramona Ilari, Francesco Lo-Coco, Ugo Testa

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

Article in Journal of hematology & oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 29% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
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 1 country.

Ernestina SaulleDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Alessia PetronelliDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Elvira PelosiDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Elena CoppotelliDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Luca PasquiniDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Ramona IlariDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Francesco Lo-CocoDepartment of Biomedicine and Prevention, University of Rome "Tor Vergata" and Fondazione Santa Lucia, Rome, Italy.
Ugo TestaDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy. ugo.testa@iss.it.
Istituto Superiore di Sanità · ITUniversity of Rome Tor Vergata · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRecent studies indicate that angiogenesis is important in the pathogenesis of acute myeloid leukemias (AMLs). Among the various AMLs, the bone marrow angiogenetic response is particularly pronounced in acute promyelocytic leukemia (APL). However, the molecular mechanisms responsible for this angiogenetic response are largely unknown. In the present study, we have explored the role of HHEX, a homeodomain transcription factor, as a possible mediator of the pro-angiogenetic response observed in APL. This transcription factor seems to represent an ideal candidate for this biologic function because it is targeted by PML-RARα, is capable of interaction with PML and PML-RARα, and acts as a regulator of the angiogenetic response.

methodsWe used various cellular systems of APL, including primary APL cells and leukemic cells engineered to express PML-RARα, to explore the role of the PML-RARα fusion protein on HHEX expression. Molecular and biochemical techniques have been used to investigate the mechanisms through which PML-RARα downmodulates HHEX and the functional consequences of this downmodulation at the level of the expression of various angiogenetic genes, cell proliferation and differentiation.

resultsOur results show that HHEX expression is clearly downmodulated in APL and that this effect is directly mediated by a repressive targeting of the HHEX gene promoter by PML-RARα. Studies carried out in primary APL cells and in a cell line model of APL with inducible PML-RARα expression directly support the view that this fusion protein through HHEX downmodulation stimulates the expression of various genes involved in angiogenesis and inhibits cell differentiation.

conclusionsOur data suggest that HHEX downmodulation by PML-RARα is a key event during APL pathogenesis.

Indexed as

Down-RegulationGene Expression Regulation, LeukemicBlotting, WesternCell DifferentiationCell Line, TumorCell ProliferationCells, CulturedHEK293 CellsHomeodomain ProteinsHumansLeukemia, Promyelocytic, AcuteNeovascularization, PathologicOncogene Proteins, FusionPromoter Regions, GeneticReverse Transcriptase Polymerase Chain ReactionTranscription FactorsHHEX protein, humanHomeodomain ProteinsOncogene Proteins, Fusionpromyelocytic leukemia-retinoic acid receptor alpha fusion oncoproteinTranscription FactorsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID27052408
PMCPMC4823896
OpenAlexW2325032490

What OpenQuestion holds

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LicenceCC BY
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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.