PXD036223

PXD036223 is an original dataset announced via ProteomeXchange.

Title	Combined proteomics and CRISPR-Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo
Description	Acute leukemias represent deadly malignancies which require better treatment. As challenge, treatment is counteracted by a microenvironment protecting dormant leukemia stem cells. To 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. A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was identified as essential vulnerability required for survival and growth of different types of acute leukemias in vivo and reconstitution assays in PDX models proved 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. These findings identify ADAM10 as attractive therapeutic target for future treatment of acute leukemias.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:04:12.711.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ashokkumar Jayavelu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; ultraflex

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-22 03:51:35	ID requested
1	2023-07-24 03:33:24	announced
⏵ 2	2023-11-14 09:04:21	announced	2023-11-14: Updated project metadata.

Bahrami E, Schmid JP, Jurinovic V, Becker M, Wirth AK, Ludwig R, Kreissig S, Duque Angel TV, Amend D, Hunt K, Ö, llinger R, Rad R, Frenz JM, Solovey M, Ziemann F, Mann M, Vick B, Wichmann C, Herold T, Jayavelu AK, Jeremias I, Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo. Mol Cancer, 22(1):107(2023) [pubmed]

submitter keyword: Leukemia Stem Cell, Proteome,ADAM10, CRISPR, Leukemia,dia PASEF

Ashok Kumar Jayavelu
contact affiliation	Proteomics and Cancer Cell Signaling Unit, German Cancer Research Center, Heidelberg,Germany
contact email	ak.jayavelu@dkfz-heidelberg.de
lab head
Ashokkumar Jayavelu
contact affiliation	Dept Proteomics and Signal Transduction, MaxPlanck Institute of Biochemistry
contact email	jayavelu@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/07/PXD036223

PRIDE project URI

• PRIDE
  1. PXD036223
     1. Label: PRIDE project
     2. Name: Combined proteomics and CRISPR-Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo