PXD017457 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
Keyword List
curator keyword: Biomedical |
submitter keyword: S100, NOTCH1,AKT, CLL, Richter syndrome |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD017457
- Label: PRIDE project
- Name: Active AKT Signaling triggers CLL towards Richter's transformation via over-activation of Notch1