PXD036918 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2023-10-24 |
AnnouncementXML | Submission_2023-10-24_10:36:10.130.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | JeroenDemmers |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: THEMIS2, biomarker, chronic lymphocytic leukemia |
Contact List
JeroenDemmers |
contact affiliation | Proteomics Center, Erasmus University Medical Center |
contact email | j.demmers@erasmusmc.nl |
lab head | |
JeroenDemmers |
contact affiliation | Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands |
contact email | j.demmers@erasmusmc.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD036918
- Label: PRIDE project
- Name: High-throughput proteomics identifies THEMIS2 as independent biomarker of inferior treatment-free survival in untreated chronic lymphocytic leukemia