title: Biological and clinical relevance of miRNA expression signatures in primary plasma cell leukemia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Hematology 1 CTMO, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Lionetti
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Di Martino
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.forename: Luca
authors.initials: L
authors.lastname: Agnelli
authors.forename: Katia
authors.initials: K
authors.lastname: Todoerti
authors.forename: Giacomo
authors.initials: G
authors.lastname: Tuana
authors.forename: Laura
authors.initials: L
authors.lastname: Mosca
authors.forename: Maria E
authors.initials: ME
authors.lastname: Gallo Cantafio
authors.forename: Vitina
authors.initials: V
authors.lastname: Grieco
authors.forename: Gabriella
authors.initials: G
authors.lastname: Bianchino
authors.forename: Fiorella
authors.initials: F
authors.lastname: D'Auria
authors.forename: Teodora
authors.initials: T
authors.lastname: Statuto
authors.forename: Carmela
authors.initials: C
authors.lastname: Mazzoccoli
authors.forename: Luciana
authors.initials: L
authors.lastname: De Luca
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Antonietta
authors.initials: A
authors.lastname: Falcone
authors.forename: Tommaso
authors.initials: T
authors.lastname: Caravita
authors.forename: Paola
authors.initials: P
authors.lastname: Omede'
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002986:Clinical Trials as Topic; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007952:Leukemia, Plasma Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs