PXD048760-2

PXD048760 is an original dataset announced via ProteomeXchange.

Title	Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2
Description	Acute myeloid leukemia (AML) driven by the activation of EVI1 due to chromosome 3q26/MECOM rearrangements is incurable with current chemotherapy regimens. Insight into the mechanism by which EVI1 drives myeloid transformation is needed to target EVI1 in those leukemias. Here we demonstrate recurrent interaction of CTBP1/2 with a unique PLDLS motif in EVI1, which is indispensable for leukemic transformation of 3q26/MECOM rearranged AML. A PLDLS competitor construct outcompetes EVI1 to CTBP1/2 binding and inhibits AML proliferation in xenotransplant models. This proof-of-concept study opens the possibility to target one of the most incurable forms of AML using specific inhibitors directed to EVI1/CTBP1/2 interaction. Our findings have important implications for other tumour types with aberrant expression of EVI1 or other oncogenic transcription factors that also depend on CTBP1/2 interaction.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:39:54.100.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Demmers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-22 04:45:06	ID requested
1	2024-05-21 07:06:03	announced
⏵ 2	2024-10-22 06:39:55	announced	2024-10-22: Updated project metadata.

10.1126/sciadv.adk9076;

Pastoors D, Havermans M, Mulet-Lazaro R, Brian D, Noort W, Grasel J, Hoogenboezem R, Smeenk L, Demmers JAA, Milsom MD, Enver T, Groen RWJ, Bindels E, Delwel R, drives acute myeloid leukemia via a targetable interaction with CTBP2. Sci Adv, 10(20):eadk9076(2024) [pubmed]

submitter keyword: CTBP2,EVI1, Acute Myeloid Leukemia

Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus MC
contact email	j.demmers@erasmusmc.nlk
lab head
Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
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/2024/05/PXD048760

PRIDE project URI

• PRIDE
  1. PXD048760
     1. Label: PRIDE project
     2. Name: Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2