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 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.

Automated summary

This study identified active promoters and alternative active promoters in different B cell subpopulations and MM patient samples, showing specific expression patterns for each subpopulation. The expression from some alternative promoters was associated with lower progression-free and overall survival in MM patients, independently of genetic alterations. These findings suggest that cancer-specific alternative active promoters could serve as new transcriptomic features for prognostic stratification in MM patients.