title: Transcriptional characterization of a prospective series of primary plasma cell leukemia revealed signatures associated with tumor progression and poorer outcome.
abstract: OBJECTIVE
  Plasma cell leukemia (PCL) is a rare form of plasma cell dyscrasia that presents either as a progression of previously diagnosed multiple myeloma, namely secondary PCL, or as initial manifestation of disease, namely primary PCL (pPCL). Although the presenting signs and symptoms include those seen in multiple myeloma, pPCL is characterized by several aspects that define a more aggressive course. Here, we have investigated the transcriptome of pPCLs and correlated differential expression profiles with outcome to provide insights into the biology of the disease.
  
  
  METHODS
  The expression profiles of 21 newly diagnosed pPCLs included in a multicenter prospective clinical trial were generated using high-density microarray, then evaluated in comparison with a representative series of patients with multiple myeloma and in association with clinical outcome.
  
  
  RESULTS
  All but one of the pPCLs had one of the main immunoglobulin heavy-chain locus translocations, whose associated transcriptional signatures resembled those observed in multiple myeloma. A 503-gene signature distinguished pPCL from multiple myeloma, from which emerged 26 genes whose expression trend was associated with progressive stages of plasma cells dyscrasia in a large dataset from multiple institutions, including samples from normal donors throughout PCL. Finally, 3 genes were identified as having expression levels that correlated with response to the first-line treatment with lenalidomide/dexamethasone, whereas a 27-gene signature was associated with overall survival independently of molecular alterations, hematologic parameters, and renal function.
  
  
  CONCLUSIONS
  Overall, our data contribute to a fine dissection of pPCL and may provide novel insights into the molecular definition of patients with poorer prognosis.
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Todoerti
authors.forename: Luca
authors.initials: L
authors.lastname: Agnelli
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.forename: Marta
authors.initials: M
authors.lastname: Lionetti
authors.forename: Giacomo
authors.initials: G
authors.lastname: Tuana
authors.forename: Laura
authors.initials: L
authors.lastname: Mosca
authors.forename: Luigia
authors.initials: L
authors.lastname: Lombardi
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: Fortunato
authors.initials: F
authors.lastname: Morabito
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: Paola
authors.initials: P
authors.lastname: Omede'
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
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
mesh_terms: D002986:Clinical Trials as Topic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007952:Leukemia, Plasma Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D057089:Pathology, Molecular; D011379:Prognosis; D016016:Proportional Hazards Models; D014158:Transcription, Genetic; D059467:Transcriptome; D016896:Treatment Outcome