Gene expression derived from alternative promoters improves prognostic stratification in multiple myeloma
Open accessAbstract
Clinical and genetic risk factors are currently used in multiple myeloma (MM) to stratify patients and to design specific therapies. However, these systems do not capture the heterogeneity of the disease supporting the development of new prognostic factors. In this study, we identified active promoters and alternative active promoters in 6 different B cell subpopulations, including bone-marrow plasma cells, and 32 MM patient samples, using RNA-seq data. We find that expression initiated at both regular and alternative promoters was specific of each B cell subpopulation or MM plasma cells, showing a remarkable level of consistency with chromatin-based promoter definition. Interestingly, using 595 MM patient samples from the CoMMpass dataset, we observed that the expression derived from some alternative promoters was associated with lower progression-free and overall survival in MM patients independently of genetic alterations. Altogether, our results define cancer-specific alternative active promoters as new transcriptomic features that can provide a new avenue for prognostic stratification possibilities in patients with MM.
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MP genes were significantly associated with OS, similar to recent observations in multiple myeloma.
“MP genes were significantly associated with OS, similar to recent observations in multiple myeloma66”
From Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes (2023) · cites this paper as [66]
The Results and discussion report that expression from alternative active promoters was significantly associated with overall survival in multiple myeloma. They do not establish that MP genes, as genes, were significantly associated with overall survival; the paper distinguishes promoter activity from overall gene expression and notes that SLAMF7 gene expression was not associated with survival. (LLM, conf=0.84)
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Research works printed but not linked: 15
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Nepal, C., & Andersen, J. B. (2023) · Nature Communications · doi:10.1038/s41467-023-38272-4 · Cited by 39 · see citing works
- Authors
- Valcárcel, L. V., Amundarain, A., Kulis, M., Charalampopoulou, S., Melnick, A., San Miguel, J., Martín-Subero, J. I., Planes, F. J., Agirre, X., & Prosper, F.
- Affiliations
- Centro de Investigación Médica Aplicada (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Fundació Clínic per a la Recerca Biomèdica (ES)
- Weill Cornell Medicine (US)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universidad de Navarra (ES)
- Corresponding author
- Planes, Francisco J.
- Agirre, Xabier
- ORCID
- Venue
- Leukemia
- Published
- 2021-05-10
- Volume
- 35
- Issue
- 10
- Pages
- 3012-3016
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- PMC
- PMC8478642
- OpenAlex
- W3162818840
- Cited by
- 17
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 2
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Leukemia (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Multiple Myeloma Research Foundation
- International Myeloma Foundation
- Fundación Ramón Areces
- Fundació la Marató de TV3 (616/C/2019)
- Ministerio de Ciencia, Innovación y Universidades
- Cancer Research UK (CIBERONC CB16/12/00489, #C355/A26819, FPU17/02733, PI17/00701, PI19/01352)
- Fonds National de la Recherche Luxembourg
- Associazione Italiana per la Ricerca sul Cancro
- Centro de Investigación Biomédica en Red de Cáncer (C355/A26819, #CB16/12/00489)
- Gobierno de Navarra
- Qatar National Research Fund (7-916-3-237)
- Instituto de Salud Carlos III (FI17/00297, PI16/, C355/A26819, PI19/01352, PI16/02024, PI16/02024, PI17/00701 and PI19/01352, Marató de TV3, PI17/00701, TRANSCAN EPICA AC16/00041, CB16/12/00489)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- multiple myeloma, alternative promoters, prognostic stratification, B cell subsets, plasma cells, progression-free survival, overall survival, transcriptomic features, gene expression
- MeSH terms
- Humans, Multiple Myeloma, Prognosis, Promoter Regions, Genetic, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Survival Rate, Gene Expression Profiling, Transcriptome
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