PXD022754

PXD022754 is an original dataset announced via ProteomeXchange.

Title	CKS1-dependent proteostatic regulation has dual roles in combating acute myeloid leukemia whilst protecting normal hematopoiesis
Description	Acute myeloid leukemia (AML) is an aggressive hematological disorder comprised of a hierarchy of quiescent leukemic stem cells and fast proliferating blasts with limited self-renewal ability. Significant plasticity in the AML epigenome and metabolome results in a high rate of drug resistance and relapse, with extremely low 2-year survival rates in the poorest cytogenetic risk patients. The current backbone of clinical induction chemotherapy reduces total disease burden, but does not deplete leukemic stem cells which reconstitute the disease in vivo, and also suffers from severe toxicity of healthy hematopoietic cells. Whilst much work has been done to identify epigenetic vulnerabilities in AML, little is known about protein dynamics, and here we explored the therapeutic inhibition of highly specific CKS1-dependent protein degradation. We report a dual role for CKS1-depdent protein degradation in specifically targeting AML, whilst protecting normal hematopoietic cells from chemotherapeutic toxicity.
HostingRepository	PRIDE
AnnounceDate	2022-07-20
AnnouncementXML	Submission_2022-07-20_08:32:30.052.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022754
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Pedro Casado-Izquierdo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-26 00:18:00	ID requested
⏵ 1	2022-07-20 08:32:30	announced

Grey W, Rio-Machin A, Casado P, Gr, ö, nroos E, Ali S, Miettinen JJ, Bewicke-Copley F, Parsons A, Heckman CA, Swanton C, Cutillas PR, Gribben J, Fitzgibbon J, Bonnet D, CKS1 inhibition depletes leukemic stem cells and protects healthy hematopoietic stem cells in acute myeloid leukemia. Sci Transl Med, 14(650):eabn3248(2022) [pubmed]

submitter keyword: CKS1, Proteostasis, AML, Hematopoiesis, Chemotherapy, Protein degradation

Pedro R. Cutillas
contact affiliation	Centre for Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London
contact email	p.cutillas@qmul.ac.uk
lab head
Pedro Casado-Izquierdo
contact affiliation	Cell Signalling
contact email	p.m.casado-izquierdo@qmul.ac.uk
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/2022/07/PXD022754

PRIDE project URI

• PRIDE
  1. PXD022754
     1. Label: PRIDE project
     2. Name: CKS1-dependent proteostatic regulation has dual roles in combating acute myeloid leukemia whilst protecting normal hematopoiesis