Gene expression derived from alternative promoters improves prognostic stratification in multiple myeloma

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 promot...

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Bibliographic Details
Published in:Leukemia 2021-10, Vol.35 (10), p.3012-3016
Main Authors: Valcárcel, Luis V., Amundarain, Ane, Kulis, Marta, Charalampopoulou, Stella, Melnick, Ari, San Miguel, Jesús, Martín-Subero, José I., Planes, Francisco J., Agirre, Xabier, Prosper, Felipe
Format: Article
Language:English
Subjects:
38/39
38/91
692/499
692/699/1541/1990/804
Biomarkers, Tumor - genetics
Bone marrow
Cancer Research
Chromatin
Critical Care Medicine
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genetic aspects
Health aspects
Hematology
Heterogeneity
Humans
Identification and classification
Intensive
Internal Medicine
Letter
Medical prognosis
Medicine
Medicine & Public Health
Multiple myeloma
Multiple Myeloma - classification
Multiple Myeloma - genetics
Multiple Myeloma - pathology
Oncology
Patients
Plasma cells
Prognosis
Promoter Regions, Genetic
Promoters
Promoters (Genetics)
Risk analysis
Risk factors
Subpopulations
Survival Rate
Transcriptome
Transcriptomics
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Summary: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.
ISSN:0887-6924
1476-5551
DOI:10.1038/s41375-021-01263-9