Abstract
Primary plasma cell leukemia (pPCL) is a rare and very aggressive form of plasma cell dyscrasia. To date, no information on microRNA (miRNA) expression in pPCL has been reported. This study aimed at investigating the involvement of miRNAs in pPCL and their possible relationship with higher tumor aggressiveness. 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 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 multiple myeloma samples. We identified a series of deregulated miRNAs in pPCL (42 upregulated and 41 downregulated) in comparison with multiple myeloma. Some of them, on the basis of their reported functions and putative target genes computed by integrative analysis, might have a role in the pathobiology of pPCL. As regards chromosomal aberrations, the expression of some miRNAs mapped to hotspot altered regions was associated with DNA copy number of the corresponding loci. Finally, 4 miRNA (miR-497, miR-106b, miR-181a*, and miR-181b) were identified as having expression levels that correlated with treatment response, and 4 (miR-92a, miR-330-3p, miR-22, and miR-146a) with clinical outcome. Overall, our study provides insights into the possible contribution of miRNAs in the pathogenesis of pPCL and suggests targets for future therapeutic investigations.
Highlights
Plasma cell leukemia (PCL) is a rare variant of multiple myeloma, characterized by poor prognosis and presence of malignant plasma cells (PCs) circulating in the peripheral blood [1]
The influence on miRNA expression of the allelic imbalances detected at DNA genome-wide level was evaluated by conducting an integrative analysis of mature miRNA expression and the inferred DNA copy number (CN) values of the corresponding miRNA gene/s available for 16 of 18 primary PCL (pPCL) cases
Taking into consideration all miRNA genes except those located on chromosome X, the expression of 23 miRNAs resulted to be significantly correlated with DNA CN on different chromosomes, with chromosome 13 (22%) and the short arm of chromosome 1 being the most involved (22%; Supplementary Table S1)
Summary
Plasma cell leukemia (PCL) is a rare variant of multiple myeloma, characterized by poor prognosis and presence of malignant plasma cells (PCs) circulating in the peripheral blood [1]. PCL can be subdivided clinically into primary and secondary types: primary PCL (pPCL) presents de novo in the leukemic phase, while secondary PCL (sPCL) arises in the context of a preexisting multiple myeloma [1]. MiRNA Expression in Primary Plasma Cell Leukemia. Plasma cell leukemia (PCL) is a very aggressive and rare hematologic malignancy that can be distinguished into primary (pPCL), originating de novo, or secondary (sPCL) malignancy, arising as a leukemic transformation of multiple myeloma. We took advantage of a prospective series of pPCL included in a phase II clinical trial to investigate global miRNA expression profiles that might reflect peculiar pathogenetic mechanisms of the disease. Since pPCL represents a high-risk clinical entity per se, biological information at diagnosis could be helpful to guide clinicians in therapeutic decisions
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