Evidence map›Paper›PMID 37420006›Full record

ArticleLeukemia2023

Activation of distinct inflammatory pathways in subgroups of LR-MDS.

Marie Schneider, Clara Rolfs, Matthias Trumpp, Susann Winter, Luise Fischer, Mandy Richter, Victoria Menger, Kolja Nenoff, Nora Grieb, Klaus H Metzeler and 11 more

Open access · hybridAbstract read
In one paragraph

Article in Leukemia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

24 citing papers in PubMed, 26 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

21 authors at 4 institutions in 3 countries.

Marie Schneider *Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.
Clara Rolfs *Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.
Matthias TrumppDepartment of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.
Susann WinterDepartment of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
Luise FischerDepartment of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
Mandy RichterDepartment of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.
Victoria MengerDepartment of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.
Kolja NenoffDepartment of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.
Nora GriebDepartment of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.
Klaus H MetzelerDepartment of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.ORCID 0000-0003-3920-7490
Anne Sophie KubaschDepartment of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.ORCID 0000-0002-0747-4941
Katja SockelDepartment of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.ORCID 0000-0003-1732-7299
Christian ThiedeDepartment of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.ORCID 0000-0003-1241-2048
Jincheng WuNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Janghee WooNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Andreas BrüderleNovartis Oncology, Basel, Switzerland.
Lorenz C HofbauerUniversityCenter for Healthy Aging & Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany.ORCID 0000-0002-8691-8423
Jörg LütznerDepartment of Orthopedic Surgery, University Hospital Carl Gustav Carus, Dresden, Germany.
Andreas RothDepartment of Orthopedic Surgery, University Medical Center Leipzig, Leipzig, Germany.
Michael Cross *Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.ORCID 0000-0002-8815-7621
Uwe Platzbecker *Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany. Uwe.Platzbecker@medizin.uni-leipzig.de.ORCID 0000-0003-1863-3239
University Hospital Leipzig · DEUniversity Hospital Carl Gustav Carus · DENovartis (United States) · USNovartis (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrant innate immune signaling has been identified as a potential key driver of the complex pathophysiology of myelodysplastic neoplasms (MDS). This study of a large, clinically and genetically well-characterized cohort of treatment-naïve MDS patients confirms intrinsic activation of inflammatory pathways in general mediated by caspase-1, interleukin (IL)-1β and IL-18 in low-risk (LR)-MDS bone marrow and reveals a previously unrecognized heterogeneity of inflammation between genetically defined LR-MDS subgroups. Principal component analysis resolved two LR-MDS phenotypes with low (cluster 1) and high (cluster 2) levels of IL1B gene expression, respectively. Cluster 1 contained 14/17 SF3B1-mutated cases, while cluster 2 contained 8/8 del(5q) cases. Targeted gene expression analysis of sorted cell populations showed that the majority of the inflammasome-related genes, including IL1B, were primarily expressed in the monocyte compartment, consistent with a dominant role in determining the inflammatory bone marrow environment. However, the highest levels of IL18 expression were found in hematopoietic stem and progenitor cells (HSPCs). The colony forming activity of healthy donor HSPCs exposed to monocytes from LR-MDS was increased by the IL-1β-neutralizing antibody canakinumab. This work reveals distinct inflammatory profiles in LR-MDS that are of likely relevance to the personalization of emerging anti-inflammatory therapies.

Indexed as

Myelodysplastic SyndromesBone MarrowGene Expression ProfilingHematopoietic Stem CellsHumansSignal Transduction

Identifiers

PMID37420006
PMCPMC10400420
OpenAlexW4383499822

What OpenQuestion holds

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LicenceCC BY
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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.