Evidence map›Paper›PMID 37422628›Full record

ArticleMolecular cancer2023

Combined proteomics and CRISPR‒Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo.

Ehsan Bahrami, Jan Philipp Schmid, Vindi Jurinovic, Martin Becker, Anna-Katharina Wirth, Romina Ludwig, Sophie Kreissig, Tania Vanessa Duque Angel, Diana Amend, Katharina Hunt and 11 more

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. CRISPR/Cas9-Mediated Genome Editing in Cancer Therapy.International journal of molecular sciences · 2023
    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

21 authors at 6 institutions in 2 countries.

Ehsan Bahrami *Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.ORCID 0000-0002-1672-5503
Jan Philipp Schmid *Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.ORCID 0009-0001-3869-8868
Vindi JurinovicResearch Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.
Martin BeckerResearch Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.ORCID 0000-0002-1751-1056
Anna-Katharina WirthResearch Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.ORCID 0000-0002-0138-8583
Romina LudwigResearch Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.
Sophie KreissigDivision of Transfusion Medicine, Cell Therapeutics and Haemostaseology, LMU University Hospital, LMU Munich, Munich, Germany.
Tania Vanessa Duque AngelResearch Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.
Diana AmendResearch Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.
Katharina HuntResearch Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.
Rupert ÖllingerCenter for Translational Cancer Research (TranslaTUM), TUM School of Medicine, and Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.ORCID 0000-0002-2292-5982
Roland RadGerman Cancer Consortium (DKTK), partner site Munich, Munich, Germany.ORCID 0000-0002-6849-9659
Joris Maximilian FrenzProteomics and Cancer Cell Signaling Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0001-8696-3817
Maria SoloveyInstitute of Computational Biology, Helmholtz Center Munich, Munich, Germany.ORCID 0009-0007-7710-9716
Frank ZiemannLaboratory for Experimental Leukemia and Lymphoma Research (ELLF), Department of Medicine III, LMU University Hospital, LMU Munich, Munich, Germany.
Matthias MannDepartment of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Munich, Germany.ORCID 0000-0003-1292-4799
Binje VickResearch Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.ORCID 0000-0003-1956-2778
Christian WichmannDivision of Transfusion Medicine, Cell Therapeutics and Haemostaseology, LMU University Hospital, LMU Munich, Munich, Germany.
Tobias HeroldResearch Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany.ORCID 0000-0002-9615-9432
Ashok Kumar Jayavelu *Proteomics and Cancer Cell Signaling Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0002-3292-1117
Irmela Jeremias *Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, Feodor-Lynen-Str. 21, Munich, 81377, Germany. Irmela.Jeremias@helmholtz-munich.de.ORCID 0000-0003-1773-7677
Helmholtz Zentrum München · DEGerman Cancer Research Center · DELudwig-Maximilians-Universität München · DETUM Klinikum · DEMax Planck Institute of Biochemistry · DEMunich Leukemia Laboratory (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAcute leukemias represent deadly malignancies that require better treatment. As a challenge, treatment is counteracted by a microenvironment protecting dormant leukemia stem cells.

methodsTo identify responsible surface proteins, we performed deep proteome profiling on minute numbers of dormant patient-derived xenograft (PDX) leukemia stem cells isolated from mice. Candidates were functionally screened by establishing a comprehensive CRISPR‒Cas9 pipeline in PDX models in vivo.

resultsA disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was identified as an essential vulnerability required for the survival and growth of different types of acute leukemias in vivo, and reconstitution assays in PDX models confirmed the relevance of its sheddase activity. Of translational importance, molecular or pharmacological targeting of ADAM10 reduced PDX leukemia burden, cell homing to the murine bone marrow and stem cell frequency, and increased leukemia response to conventional chemotherapy in vivo.

conclusionsThese findings identify ADAM10 as an attractive therapeutic target for the future treatment of acute leukemias.

Indexed as

LeukemiaProteomicsADAM10 ProteinAmyloid Precursor Protein SecretasesAnimalsCRISPR-Cas SystemsDisease Models, AnimalHumansMembrane ProteinsMiceTumor MicroenvironmentADAM10 ProteinADAM10 protein, humanAmyloid Precursor Protein SecretasesMembrane ProteinsAcute leukemiaADAM10CRISPR-Cas9 in vivo screenLeukemia stem cellsPDXProteomics

Identifiers

PMID37422628
PMCPMC10329331
OpenAlexW4383620086

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.