Biological and clinical relevance of miRNA expression signatures in primary plasma cell leukemia

PURPOSE: Primary plasma cell leukemia (pPCL) is a rare and very aggressive form of plasma cell dyscrasia. To date, no information on miRNA expression in pPCL has been reported. This study was aimed at investigating the involvement of miRNAs in pPCL and their possible relationship with higher tumor aggressiveness. Experimental design: Global miRNA expression profiles were analyzed in highly-purified malignant plasma cells from 18 pPCL untreated patients included in a prospective clinical trial. MiRNA expression patterns were evaluated in comparison with a representative series of multiple myeloma (MM) patients, in relation to the most recurrent chromosomal abnormalities (as assessed by fluorescence in situ hybridization and single nucleotide polymorphism-array analysis), and in association with clinical outcome. MiRNA expression was also integrated with gene expression profiles in pPCL and MM samples. RESULTS: We identified a series of deregulated miRNAs in pPCL (42 up- and 41 down-regulated) in comparison with MM. Some of them, based on their reported functions and putative target genes computed by integrative analysis, might have a role in the pathobiology of pPCL. As regards to chromosomal aberrations, the expression of some miRNAs mapped to hot-spot altered regions was associated with DNA copy number of the corresponding loci. Finally, four miRNA (miR-497, miR-106b, miR-181a* and miR-181b) were identified having expression levels correlated with treatment response, and four (miR-92a, miR-330-3p, miR-22, and miR-146a) with clinical outcome. CONCLUSIONS: Overall, our study provides insights into the possible contribution of miRNAs in the pathogenesis of pPCL and suggests targets for future therapeutic investigations