PXD011359

PXD011359 is an original dataset announced via ProteomeXchange.

Title	The p30 isoform of CEBPA uncovers a silent enhancer to drive the expression of the tumor promoting factor CD73 in CEBPA mutant AML
Description	The key myeloid transcription factor (TF) CEBPA is frequently mutated in acute myeloid leukemia (AML), but the molecular ramifications of this leukemic driver mutation remain elusive. To investigate CEBPA mutant AML, we compared gene expression changes in human CEBPA mutant AML and in the corresponding CebpaLp30 mouse model, and identified a conserved cross-species transcriptional program. ChIP-seq revealed aberrantly activated enhancers, exclusively occupied by the leukemia-associated CEBPA-p30 isoform. One leukemic-enhancer upstream of Nt5e, encoding CD73, was physically and functionally linked to this conserved AML gene, and could be activated by CEBPA. Targeting of CD73-adenosine signaling increased AML survival in transplanted mice. Our data indicate a first-in-class link between a TF cancer driver mutation and a druggable, direct transcriptional target.
HostingRepository	PRIDE
AnnounceDate	2019-08-08
AnnouncementXML	Submission_2019-08-08_07:42:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Erwin Schoof
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-15 07:35:02	ID requested
⏵ 1	2019-08-08 07:42:38	announced

Jakobsen JS, Laursen LG, Schuster MB, Pundhir S, Schoof E, Ge Y, d'Altri T, Vitting-Seerup K, Rapin N, Gentil C, Jendholm J, Theilgaard-M, ö, nch K, Reckzeh K, Bullinger L, D, ö, hner K, Hokland P, Fitzgibbon J, Porse BT, Mutant CEBPA directly drives the expression of the targetable tumor-promoting factor CD73 in AML. Sci Adv, 5(7):eaaw4304(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: CEBPA, global proteomics, acute myeloid leukemia

Bo T. Porse
contact affiliation	1The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; 2Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark; 3Danish Stem Cell Centre (DanStem) Faculty of Health Sciences, University of Copenhagen, Denmark
contact email	shb244@ku.dk
lab head
Erwin Schoof
contact affiliation	Technical University of Denmark
contact email	erws@dtu.dk
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/2019/08/PXD011359

PRIDE project URI

• PRIDE
  1. PXD011359
     1. Label: PRIDE project
     2. Name: The p30 isoform of CEBPA uncovers a silent enhancer to drive the expression of the tumor promoting factor CD73 in CEBPA mutant AML