PXD036075 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Clinical drug response and proteotype profiling elucidates targetable vulnerabilities of myelofibrosis |
Description | Myelofibrosis (MF) is a hematopoietic stem cell disorder belonging to the myeloproliferative neoplasms. MF patients frequently carry driver mutations in JAK2 and Calreticulin (CALR) and have limited therapeutic options. Here, we integrate ex vivo drug response and proteotype analyses across MF patient cohorts to discover targetable vulnerabilities and associated therapeutic strategies. Drug sensitivities of mutated and progenitor cells were measured in patient blood using high-content imaging and single-cell deep learning-based analyses. Integration with matched molecular profiling revealed three therapeutic vulnerabilities. First, CALR mutations drive BET and HDAC inhibitor sensitivity, particularly in the absence of high MAPK-Ras pathway protein levels. Second, an MCM complex-high proliferative signature corresponds to advanced disease and sensitivity to drugs targeting pro-survival signaling and DNA replication. Third, homozygous CALR mutations result in high ER stress, responding to ER stressors and UPR inhibition. Overall, our integrated analyses provide a molecularly-motivated roadmap for individualized MF patient treatment. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:29:54.620.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Mattheus Wildschut |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos; Q Exactive HF-X; Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-08-16 05:34:00 | ID requested | |
1 | 2023-10-14 18:11:16 | announced | |
⏵ 2 | 2023-11-14 08:29:55 | announced | 2023-11-14: Updated project metadata. |
3 | 2024-10-22 06:05:59 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Drug screening,Myelofibrosis, Patient samples, Granulocytes, T-cells, Proteotyping, HSPCs |
Contact List
Berend Snijder |
contact affiliation | Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland |
contact email | snijder@imsb.biol.ethz.ch |
lab head | |
Mattheus Wildschut |
contact affiliation | ETH Zurich / University Hospital Zurich |
contact email | wildschut@imsb.biol.ethz.ch |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD036075
- Label: PRIDE project
- Name: Clinical drug response and proteotype profiling elucidates targetable vulnerabilities of myelofibrosis