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

Marta Lionetti, Pellegrino Musto, Maria Teresa Di Martino, Sonia Fabris, Luca Agnelli, Katia Todoerti, Giacomo Tuana, Laura Mosca, Maria E Gallo Cantafio, Vitina Grieco, Gabriella Bianchino, Fiorella D'Auria, Teodora Statuto, Carmela Mazzoccoli, Luciana De Luca, Maria Teresa Petrucci, Massimo Offidani, Francesco Di Raimondo, Antonietta Falcone, Tommaso CaravitaPaola Omede, Fortunato Morabito, Pierfrancesco Tassone, Mario Boccadoro, Antonio Palumbo, Antonino Neri

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Abstract

Purpose: 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. 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 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. Results: 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. Conclusions: Overall, our study provides insights into the possible contribution of miRNAs in the pathogenesis of pPCL and suggests targets for future therapeutic investigations.

Original languageEnglish
Pages (from-to)3130-3142
Number of pages13
JournalClinical Cancer Research
Volume19
Issue number12
DOIs
Publication statusPublished - Jun 15 2013

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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