دورية أكاديمية
High-throughput Proteomics Identifies THEMIS2 as Independent Biomarker of Treatment-free Survival in Untreated CLL
| العنوان: | High-throughput Proteomics Identifies THEMIS2 as Independent Biomarker of Treatment-free Survival in Untreated CLL |
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| المؤلفون: | Paul J. Hengeveld, P. Martijn Kolijn, Jeroen A.A. Demmers, Wouter Doff, Julie M.N. Dubois, Melissa Rijken, Jorn L.J.C. Assmann, Lina van der Straten, Henk Jan Boiten, Kirsten J. Gussinklo, Peter J.M. Valk, Laura M. Faber, Peter E. Westerweel, Arnon P. Kater, Mark-David Levin, Anton W. Langerak |
| المصدر: | HemaSphere, Vol 7, Iss 10, p e951 (2023) |
| بيانات النشر: | Wiley, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | It remains challenging in chronic lymphocytic leukemia (CLL) to distinguish between patients with favorable and unfavorable time-to-first treatment (TTFT). Additionally, the downstream protein correlates of well-known molecular features of CLL are not always clear. To address this, we selected 40 CLL patients with TTFT ≤24 months and compared their B cell intracellular protein expression with 40 age- and sex-matched CLL patients with TTFT >24 months using mass spectrometry. In total, 3268 proteins were quantified in the cohort. Immunoglobulin heavy-chain variable (IGHV) mutational status and trisomy 12 were most impactful on the CLL proteome. Comparing cases to controls, 5 proteins were significantly upregulated, whereas 3 proteins were significantly downregulated. Of these, only THEMIS2, a signaling protein acting downstream of the B cell receptor, was significantly associated with TTFT, independently of IGHV and TP53 mutational status (hazard ratio, 2.49 [95% confidence interval, 1.62-3.84]; P < 0.001). This association was validated on the mRNA and protein level by quantitative polymerase chain reaction and ELISA, respectively. Analysis of 2 independently generated RNA sequencing and mass spectrometry datasets confirmed the association between THEMIS2 expression and clinical outcome. In conclusion, we present a comprehensive characterization of the proteome of untreated CLL and identify THEMIS2 expression as a putative biomarker of TTFT. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2572-9241 00000000 |
| Relation: | http://journals.lww.com/10.1097/HS9.0000000000000951; https://doaj.org/toc/2572-9241 |
| DOI: | 10.1097/HS9.0000000000000951 |
| URL الوصول: | https://doaj.org/article/9c7c2aec214047bd85fc59184f7b706f |
| رقم الأكسشن: | edsdoj.9c7c2aec214047bd85fc59184f7b706f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 25729241 00000000 |
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| DOI: | 10.1097/HS9.0000000000000951 |