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PXD017457

PXD017457 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleActive AKT Signaling triggers CLL towards Richter's transformation via over-activation of Notch1
DescriptionRichter'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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:19:29.232.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJanica Wiederstein
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-02-11 08:20:44ID requested
12021-02-25 08:07:25announced
22024-10-22 05:19:30announced2024-10-22: Updated project metadata.
Publication List
10.1182/blood.2020005734;
Keyword List
curator keyword: Biomedical
submitter keyword: S100, NOTCH1,AKT, CLL, Richter syndrome
Contact List
Thomas Wunderlich
contact affiliationMax Planck Institute for Metabolism Research Cologne, 50931 Cologne, Germany
contact emailthomas.wunderlich@sf.mpg.de
lab head
Janica Wiederstein
contact affiliationInstitute for Genetics/CECAD (AG Krüger)
contact emailjwieders@uni-koeln.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
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