Evidence map›Paper›PMID 24658077›Full record

ArticleNature medicine2014

An activin receptor IIA ligand trap corrects ineffective erythropoiesis in β-thalassemia.

Michael Dussiot, Thiago T Maciel, Aurélie Fricot, Céline Chartier, Olivier Negre, Joel Veiga, Damien Grapton, Etienne Paubelle, Emmanuel Payen, Yves Beuzard and 11 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 2 pooled it
17.1field-weighted citation impact, top 1% 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

147 citing papers in PubMed, 2 syntheses or guidelines pooled it, 270 citations in OpenAlex.

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  6. A variant erythroferrone disrupts iron homeostasis inScience translational medicine · 2019
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87 more citing papers are in PubMed but not listed here.

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

21 authors at 4 institutions in 2 countries.

Michael Dussiot1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France. [5] INSERM U1149, Center for Research on Inflammation, Paris, France. [6].
Thiago T Maciel1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France. [5] INSERM U1149, Center for Research on Inflammation, Paris, France. [6].
Aurélie Fricot1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France. [5] INSERM U1149, Center for Research on Inflammation, Paris, France.
Céline Chartier1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France. [5] INSERM U1149, Center for Research on Inflammation, Paris, France.
Olivier Negre1] Commissariat à l'Energie Atomique (CEA)-Institut des Maladies Emergentes et des Thérapies Innovantes (iMETI), Fontenay-aux-Roses, France. [2] UMR 962 (Inserm-CEA-University of Paris-Sud), Fontenay-aux-Roses, France.
Joel VeigaLaboratory of Excellence GR-Ex, Paris, France.
Damien Grapton1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France. [5] INSERM U1149, Center for Research on Inflammation, Paris, France.
Etienne Paubelle1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France. [5] INSERM U1149, Center for Research on Inflammation, Paris, France.
Emmanuel Payen1] Commissariat à l'Energie Atomique (CEA)-Institut des Maladies Emergentes et des Thérapies Innovantes (iMETI), Fontenay-aux-Roses, France. [2] UMR 962 (Inserm-CEA-University of Paris-Sud), Fontenay-aux-Roses, France.
Yves Beuzard1] Commissariat à l'Energie Atomique (CEA)-Institut des Maladies Emergentes et des Thérapies Innovantes (iMETI), Fontenay-aux-Roses, France. [2] UMR 962 (Inserm-CEA-University of Paris-Sud), Fontenay-aux-Roses, France.
Philippe Leboulch1] Commissariat à l'Energie Atomique (CEA)-Institut des Maladies Emergentes et des Thérapies Innovantes (iMETI), Fontenay-aux-Roses, France. [2] UMR 962 (Inserm-CEA-University of Paris-Sud), Fontenay-aux-Roses, France.
Jean-Antoine Ribeil1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France. [5] Département de Biothérapie, Hôpital Necker-Enfants Malades, Paris, France.
Jean-Benoit Arlet1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France.
Francine Coté1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France.
Geneviève Courtois1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France.
Yelena Z GinzburgErythropoiesis Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.
Thomas O DanielCelgene, Summit, New Jersey, USA.
Rajesh ChopraCelgene, Summit, New Jersey, USA.
Victoria SungCelgene, San Francisco, California, USA.
Olivier Hermine1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France. [5] Service d'Hématologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France.
Ivan C Moura1] INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France. [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. [3] CNRS ERL 8254, Paris, France. [4] Laboratory of Excellence GR-Ex, Paris, France. [5] INSERM U1149, Center for Research on Inflammation, Paris, France.ORCID 0000000284182803
Délégation Paris 5 · FRUniversité Paris-Sud · FRLaboratory of Excellence GR-Ex · FRNew York Blood Center · US

Funding

Regulatory Role of Transferrin in Erythropoiesis and Iron MetabolismR01DK095112 · NIDDK · SAINT LOUIS UNIVERSITY · PI Robert E Fleming, Yelena Ginzburg · 2012 to 2026
$5.4M
Understanding and Improving Iron Distribution and Erythropoiesis in Beta-ThalasseK08HL105682 · NHLBI · NEW YORK BLOOD CENTER · PI GINZBURG, YELENA · 2011 to 2015
$661k
NHLBI NIH HHS K08 HL105682NIDDK NIH HHS R01 DK095112
6 · The paper itself

Abstract

The pathophysiology of ineffective erythropoiesis in β-thalassemia is poorly understood. We report that RAP-011, an activin receptor IIA (ActRIIA) ligand trap, improved ineffective erythropoiesis, corrected anemia and limited iron overload in a mouse model of β-thalassemia intermedia. Expression of growth differentiation factor 11 (GDF11), an ActRIIA ligand, was increased in splenic erythroblasts from thalassemic mice and in erythroblasts and sera from subjects with β-thalassemia. Inactivation of GDF11 decreased oxidative stress and the amount of α-globin membrane precipitates, resulting in increased terminal erythroid differentiation. Abnormal GDF11 expression was dependent on reactive oxygen species, suggesting the existence of an autocrine amplification loop in β-thalassemia. GDF11 inactivation also corrected the abnormal ratio of immature/mature erythroblasts by inducing apoptosis of immature erythroblasts through the Fas-Fas ligand pathway. Taken together, these observations suggest that ActRIIA ligand traps may have therapeutic relevance in β-thalassemia by suppressing the deleterious effects of GDF11, a cytokine which blocks terminal erythroid maturation through an autocrine amplification loop involving oxidative stress and α-globin precipitation.

Indexed as

Activin Receptors, Type IIAnimalsApoptosisAutocrine Communicationbeta-ThalassemiaBone Morphogenetic ProteinsCell DifferentiationDisease Models, AnimalErythroblastsErythropoiesisFas Ligand Proteinfas ReceptorGene AmplificationGrowth Differentiation FactorsHematinicsLigandsActivin Receptors, Type IIactivin receptor type II-ABone Morphogenetic ProteinsFas Ligand Proteinfas ReceptorGDF11 protein, humanGdf11 protein, mouseGrowth Differentiation FactorsHematinicsLigandsReactive Oxygen SpeciesRecombinant Fusion Proteinssotatercept

Identifiers

PMID24658077
PMCPMC7730561
OpenAlexW2149986474

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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.