Evidence map›Paper›PMID 36932114›Full record

ArticleNature communications2023

Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies.

Qingyu Xu, Alexander Streuer, Johann-Christoph Jann, Eva Altrock, Nanni Schmitt, Johanna Flach, Carla Sens-Albert, Felicitas Rapp, Julia Wolf, Verena Nowak and 22 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Haematologica · 2024
    Article
  4. Review
  5. 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

32 authors.

Qingyu XuDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Alexander StreuerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.ORCID 0000-0002-3531-534X
Johann-Christoph JannDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Eva AltrockDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Nanni SchmittDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.ORCID 0000-0003-3455-9606
Johanna FlachDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Carla Sens-AlbertDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Felicitas RappDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.ORCID 0000-0003-0968-1546
Julia WolfDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Verena NowakDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Nadine WeimerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Julia ObländerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Iris PalmeDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Mariia KuzinaInstitute of Biological and Chemical Systems - Functional Molecular Systems, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, 76344, Germany.ORCID 0000-0003-4278-1071
Ahmed JawharDepartment of Orthopedic Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Ali DarwichDepartment of Orthopedic Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Cleo-Aron WeisInstitute of Pathology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Alexander MarxInstitute of Pathology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.ORCID 0000-0001-9722-2483
Patrick WuchterInstitute of Transfusion Medicine and Immunology, German Red Cross Blood Service Baden-Württemberg-Hessen, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Victor CostinaInstitute of Clinical Chemistry, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Evelyn JägerInstitute of Clinical Chemistry, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Elena SperkDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.ORCID 0000-0002-8771-8124
Michael NeumaierInstitute of Clinical Chemistry, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.ORCID 0000-0003-0410-3931
Alice FabariusDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Georgia MetzgerothDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Florian NolteDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Laurenz SteinerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Pavel A LevkinInstitute of Biological and Chemical Systems - Functional Molecular Systems, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, 76344, Germany.ORCID 0000-0002-5975-948X
Mohamad JawharDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Wolf-Karsten HofmannDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Vladimir Riabov *Department of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany. vladimir.ryabov@medma.uni-heidelberg.de.ORCID 0000-0001-5689-5681
Daniel Nowak *Department of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany. daniel.nowak@medma.uni-heidelberg.de.ORCID 0000-0001-7130-7921

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration of erythroid differentiation in hematopoietic stem and progenitor cells (HSPCs) of MN patients in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5-AZA alone. This effect requires direct contact of HSPCs with bone marrow stroma components and is dependent on integrin signaling. We further confirm these results in vivo using a bone marrow niche-dependent MN xenograft model in female NSG mice, in which we additionally demonstrate an enforced reduction of dominant clones as well as significant attenuation of disease expansion and normalization of spleen sizes. Overall, these results lay out a strong pre-clinical rationale for efficacy of combination treatment of 5-AZA with PXS-5505 especially for anemic MN.

Indexed as

Myelodysplastic SyndromesMyeloproliferative DisordersNeoplasmsAnimalsAzacitidineErythropoiesisFemaleHematopoietic Stem CellsHumansMiceProtein-Lysine 6-OxidaseAzacitidineProtein-Lysine 6-Oxidase

Identifiers

PMID36932114
PMCPMC10023686

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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.