PXD024544

PXD024544 is an original dataset announced via ProteomeXchange.

Title	Proteogenomic subtyping of chronic lymphocytic leukemia identifies subgroups with contrasting clinical outcome and distinct ex-vivo drug response profile – DIA Validation
Description	We have performed a comprehensive proteomic analysis of clinical patient samples of chronic lymphocytic leukemia (CLL) alongside genome-, transcriptome- and ex-vivo drug response profiling. Trisomy 12 and IGHV mutation status had the strongest impact on the proteome and transcriptome; and SF3B1 mutations preferentially affected the proteome. Unsupervised clustering of the proteome data partitioned CLL patients into six protein based subgroups (PG) with contrasting clinical behavior. PG1-4 could be explained by the impact of trisomy 12 and IGHV mutation status on protein abundances and another subgroup (PG6), was enriched for TP53 mutations. In addition we uncovered a new subgroup (PG5) only detectable from the proteome, characterized by low expression of central B-cell receptor proteins, altered splicing, metabolic reprogramming and increased sensitivity to proteasomal inhibition. We further validated the existence of this subgroup by conducting DIA based proteomics of an additional 167 patients. This entry contains the DIA-data for 167 patients used to validate the subgroups identified using HiRIEF-LC-MS/MS (see separate accession: PXD017453) as well as DIA data for 36 of the original discovery cohort. https://www.ebi.ac.uk/pride/archive/projects/PXD028936
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:35:33.135.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Georgios Mermelekas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-05 03:11:22	ID requested
1	2022-10-19 12:06:00	announced
⏵ 2	2023-11-14 07:35:34	announced	2023-11-14: Updated project metadata.

Herbst SA, Vesterlund M, Helmboldt AJ, Jafari R, Siavelis I, Stahl M, Schitter EC, Liebers N, Brinkmann BJ, Czernilofsky F, Roider T, Bruch PM, Iskar M, Kittai A, Huang Y, Lu J, Richter S, Mermelekas G, Umer HM, Knoll M, Kolb C, Lenze A, Cao X, Ö, sterholm C, Wahnschaffe L, Herling C, Scheinost S, Ganzinger M, Mansouri L, Kriegsmann K, Kriegsmann M, Anders S, Zapatka M, Del Poeta G, Zucchetto A, Bomben R, Gattei V, Dreger P, Woyach J, Herling M, M, ü, ller-Tidow C, Rosenquist R, Stilgenbauer S, Zenz T, Huber W, Tausch E, Lehti, ö J, Dietrich S, Proteogenomics refines the molecular classification of chronic lymphocytic leukemia. Nat Commun, 13(1):6226(2022) [pubmed]

submitter keyword: Lymphoblast, B-cell, Chronic Lymphoblastic Leukemia, Human,Leukemia, Cancer, Proteogenomics, HiRIEF, DIA, LC-MS, Clinical samples, Data Independent Acquisition, Proteomics

Janne Lehtiö
contact affiliation	Dept. Oncology Pathology, Karolinska Institutet, and Scilifelab, Stockholm, Sweden
contact email	janne.lehtio@ki.se
lab head
Georgios Mermelekas
contact affiliation	Karolinska Institutet
contact email	georgios.mermelekas@scilifelab.se
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/2022/10/PXD024544

PRIDE project URI

• PRIDE
  1. PXD024544
     1. Label: PRIDE project
     2. Name: Proteogenomic subtyping of chronic lymphocytic leukemia identifies subgroups with contrasting clinical outcome and distinct ex-vivo drug response profile – DIA Validation