PXD017457

PXD017457 is an original dataset announced via ProteomeXchange.

Title	Active AKT Signaling triggers CLL towards Richter's transformation via over-activation of Notch1
Description	Richter's syndrome (RS) is an aggressive transformation of Chronic Lymphocytic Leukaemia (CLL) frequently due to TP53, CDKN2, MYC or NOTCH1 mutations. whereas a significant proportion displays no specifically acquired driver mutation. We observe constitutive AKT phosphorylation not only in high-risk CLL patients harbouring p53 and NOTCH mutations but also in numerous RS patients. Consistently, genetic over-activation of AKT within the Eµ-TCL1 CLL mouse model results in a high-grade lymphoma phenotype of Richters syndrome. Multiomics assessment of our novel mouse model revealed a S100 defined subcluster of highly proliferative lymphoma cells developing from indolent CLL-like B-cells as a consequence of sudden NOTCH activation being fueled by enhanced NOTCH ligand exposure from T-cells in the microenvironment. Our data link AKT and NOTCH signaling in patient samples, genomic alterations, phosphoproteome and single-cell transcriptome profiles. Collectively, we have identified active AKT as a causative transforming pathway of indolent CLL towards aggressive RS thus providing novel mechanistic insights into the molecular understanding of RS.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:19:29.232.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Janica Wiederstein
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-11 08:20:44	ID requested
1	2021-02-25 08:07:25	announced
⏵ 2	2024-10-22 05:19:30	announced	2024-10-22: Updated project metadata.

10.1182/blood.2020005734;

curator keyword: Biomedical

submitter keyword: S100, NOTCH1,AKT, CLL, Richter syndrome

Thomas Wunderlich
contact affiliation	Max Planck Institute for Metabolism Research Cologne, 50931 Cologne, Germany
contact email	thomas.wunderlich@sf.mpg.de
lab head
Janica Wiederstein
contact affiliation	Institute for Genetics/CECAD (AG Krüger)
contact email	jwieders@uni-koeln.de
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/2021/02/PXD017457

PRIDE project URI

• PRIDE
  1. PXD017457
     1. Label: PRIDE project
     2. Name: Active AKT Signaling triggers CLL towards Richter's transformation via over-activation of Notch1