PXD036223 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: Leukemia Stem Cell, Proteome,ADAM10, CRISPR, Leukemia,dia PASEF |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD036223
- Label: PRIDE project
- Name: Combined proteomics and CRISPR-Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo