Evidence map›Paper›PMID 34172896›Full record

ArticleLeukemia2022

Preclinical evaluation of eltrombopag in a PDX model of myelodysplastic syndromes.

Nanni Schmitt, Johann-Christoph Jann, Eva Altrock, Johanna Flach, Justine Danner, Stefanie Uhlig, Alexander Streuer, Antje Knaflic, Vladimir Riabov, Qingyu Xu and 17 more

Open access · hybridAbstract readEvaluation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

8 citing papers in PubMed, 8 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

27 authors at 1 institution in 1 country.

Nanni SchmittDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Johann-Christoph JannDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Eva AltrockDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Johanna FlachDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Justine DannerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Stefanie UhligFlow Core Mannheim and Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Alexander StreuerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Antje KnaflicDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Vladimir RiabovDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Qingyu XuDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Arwin MehralivandDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0002-2397-8955
Iris PalmeDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Verena NowakDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Julia ObländerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Nadine WeimerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Verena HaselmannInstitute of Clinical Chemistry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Ahmed JawharDepartment of Orthopedics and Traumatology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Ali DarwichDepartment of Orthopedics and Traumatology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Cleo-Aron WeisInstitute of Pathology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Alexander MarxInstitute of Pathology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Laurenz SteinerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0002-4524-037X
Mohamad JawharDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Georgia MetzgerothDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Tobias BochDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Florian NolteDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Wolf-Karsten HofmannDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Daniel NowakDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. daniel.nowak@medma.uni-heidelberg.de.ORCID http://orcid.org/0000-0001-7130-7921
Heidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Preclinical research of myelodysplastic syndromes (MDSs) is hampered by a lack of feasible disease models. Previously, we have established a robust patient-derived xenograft (PDX) model for MDS. Here we demonstrate for the first time that this model is applicable as a preclinical platform to address pending clinical questions by interrogating the efficacy and safety of the thrombopoietin receptor agonist eltrombopag. Our preclinical study included n = 49 xenografts generated from n = 9 MDS patient samples. Substance efficacy was evidenced by FACS-based human platelet quantification and clonal bone marrow evolution was reconstructed by serial whole-exome sequencing of the PDX samples. In contrast to clinical trials in humans, this experimental setup allowed vehicle- and replicate-controlled analyses on a patient-individual level deciphering substance-specific effects from natural disease progression. We found that eltrombopag effectively stimulated thrombopoiesis in MDS PDX without adversely affecting the patients' clonal composition. In conclusion, our MDS PDX model is a useful tool for testing new therapeutic concepts in MDS preceding clinical trials.

Indexed as

AgedAged, 80 and overAnimalsApoptosisBenzoatesCell ProliferationFemaleHumansHydrazinesMaleMiceMice, Inbred NODMice, SCIDMiddle AgedMyelodysplastic SyndromesPrognosisBenzoateseltrombopagHydrazinesPyrazoles

Identifiers

PMID34172896
PMCPMC8727300
OpenAlexW3176423336

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.