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.
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 myelomapatients, 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.
Authors: P Musto; V Simeon; M C Martorelli; M T Petrucci; N Cascavilla; F Di Raimondo; T Caravita; F Morabito; M Offidani; A Olivieri; G Benevolo; R Mina; R Guariglia; G D'Arena; G Mansueto; N Filardi; F Nobile; A Levi; A Falcone; M Cavalli; G Pietrantuono; O Villani; S Bringhen; P Omedè; R Lerose; L Agnelli; K Todoerti; A Neri; M Boccadoro; A Palumbo Journal: Leukemia Date: 2013-08-20 Impact factor: 11.528
Authors: Johannes M Waldschmidt; Tushara Vijaykumar; Birgit Knoechel; Jens G Lohr Journal: Best Pract Res Clin Haematol Date: 2020-01-14 Impact factor: 3.020
Authors: Nina A Sibbesen; Katharina L Kopp; Ivan V Litvinov; Lars Jønson; Andreas Willerslev-Olsen; Simon Fredholm; David L Petersen; Claudia Nastasi; Thorbjørn Krejsgaard; Lise M Lindahl; Robert Gniadecki; Nigel P Mongan; Denis Sasseville; Mariusz A Wasik; Lars Iversen; Charlotte M Bonefeld; Carsten Geisler; Anders Woetmann; Niels Odum Journal: Oncotarget Date: 2015-08-21