PXD036918

PXD036918 is an original dataset announced via ProteomeXchange.

Title	High-throughput proteomics identifies THEMIS2 as independent biomarker of inferior treatment-free survival in untreated chronic lymphocytic leukemia
Description	Notwithstanding advances in the prognostication of chronic lymphocytic leukemia (CLL), it remains challenging to distinguish between patients with favorable and unfavorable treatment-free survival (TFS). Additionally, the downstream protein correlates of well-known molecular features of CLL are not always clear. To address this, we performed large-scale, unbiased characterization of global intracellular protein expression in a cohort of 40 CLL cases (patients with time to first treatment [TTFT] ≤24 months of sampling) and 40 age- and sex-matched CLL controls (patients with TTFT >24 months since sampling). Expression of 3268 proteins was quantified in the cohort. IGHV mutational status and trisomy 12 were most impactful on the CLL proteome. Intriguingly, comparing our results to three recently performed CLL mass-spectrometry screens, we identified four proteins that are strongly and consistently associated with IGHV mutational status: ZAP70, LMNA, FTL and FTH1. Additionally, we found that high intracellular protein levels of THEMIS2, a signaling protein acting downstream of the B-cell receptor, was significantly associated with short TTFT, independently of IGHV and TP53 mutational status (HR 2.47 [95%CI 1.54-3.95], P<0.01). This association was validated on the mRNA and protein level by qPCR and ELISA, respectivelly. Lastly, analysis of an independently generated CLL mass-spectrometry dataset verified the association between THEMIS2 expression and TFS (high THEMIS2, median TFS 4 months, versus low THEMIS2, median TFS not reached, P<0.0001)3. In conclusion, we present a comprehensive characterization of the proteome of untreated CLL. Of note, we identify elevated gene and protein expression of THEMIS2 as putative biomarker of inferior TTFT.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:06:43.005.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Demmers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-21 15:19:04	ID requested
1	2023-10-24 10:36:10	announced
⏵ 2	2023-11-14 09:06:51	announced	2023-11-14: Updated project metadata.

Hengeveld PJ, Kolijn PM, Demmers JAA, Doff W, Dubois JMN, Rijken M, Assmann JLJC, van der Straten L, Boiten HJ, Gussinklo KJ, Valk PJM, Faber LM, Westerweel PE, Kater AP, Levin MD, Langerak AW, High-throughput Proteomics Identifies THEMIS2 as Independent Biomarker of Treatment-free Survival in Untreated CLL. Hemasphere, 7(10):e951(2023) [pubmed]

submitter keyword: THEMIS2, biomarker, chronic lymphocytic leukemia

Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center
contact email	j.demmers@erasmusmc.nl
lab head
Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
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/2023/10/PXD036918

PRIDE project URI

• PRIDE
  1. PXD036918
     1. Label: PRIDE project
     2. Name: High-throughput proteomics identifies THEMIS2 as independent biomarker of inferior treatment-free survival in untreated chronic lymphocytic leukemia