title: Transcriptome analysis reveals molecular profiles associated with evolving steps of monoclonal gammopathies.
abstract: A multistep model has been proposed of disease progression starting in monoclonal gammopathy of undetermined significance continuing through multiple myeloma, sometimes with an intermediate entity called smoldering myeloma, and ending in extramedullary disease. To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell to a clonal plasma cell, and from an indolent clonal plasma cell to a malignant plasma cell, we performed gene expression profiling in 20 patients with monoclonal gammopathy of undetermined significance, 33 with high-risk smoldering myeloma and 41 with multiple myeloma. The analysis showed that 126 genes were differentially expressed in monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma as compared to normal plasma cell. Interestingly, 17 and 9 out of the 126 significant differentially expressed genes were small nucleolar RNA molecules and zinc finger proteins. Several proapoptotic genes (AKT1 and AKT2) were down-regulated and antiapoptotic genes (APAF1 and BCL2L1) were up-regulated in multiple myeloma, both symptomatic and asymptomatic, compared to monoclonal gammopathy of undetermined significance. When we looked for those genes progressively modulated through the evolving stages of monoclonal gammopathies, eight snoRNA showed a progressive increase while APAF1, VCAN and MEGF9 exhibited a progressive downregulation. In conclusion, our data show that although monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma are not clearly distinguishable groups according to their gene expression profiling, several signaling pathways and genes were significantly deregulated at different steps of the transformation process.
authors.affiliation: Servicio de Hematología del Hospital Universitario de Salamanca, IBSAL IBMCC (USAL-CSIC), Salamanca lucialopezcorral@usal.es.
authors.forename: Lucía
authors.initials: L
authors.lastname: López-Corral
authors.affiliation: Servicio de Hematología del Hospital Universitario de Salamanca, IBSAL IBMCC (USAL-CSIC), Salamanca.
authors.forename: Luis Antonio
authors.initials: LA
authors.lastname: Corchete
authors.affiliation: Servicio de Hematología del Hospital Universitario de Salamanca, IBSAL IBMCC (USAL-CSIC), Salamanca.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Sarasquete
authors.affiliation: Servicio de Hematología del Hospital Universitario de Salamanca, IBSAL IBMCC (USAL-CSIC), Salamanca.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Servicio de Hematología del Hospital Universitario de Salamanca, IBSAL IBMCC (USAL-CSIC), Salamanca.
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.affiliation: Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca.
authors.forename: Encarna
authors.initials: E
authors.lastname: Fermiñán
authors.affiliation: Servicio de Hematología del Hospital 12 de Octubre, Madrid.
authors.forename: Juan-José
authors.initials: JJ
authors.lastname: Lahuerta
authors.affiliation: Servicio de Hematología del Hospital Clinic, Barcelona.
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.affiliation: Servicio de Hematología del Hospital Germans Trias i Pujol, Badalona.
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Servicio de Hematología del Hospital Universitario de Valencia.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Teruel
authors.affiliation: Servicio de Hematología del Hospital Virgen del Rocío, Sevilla.
authors.forename: María Luz
authors.initials: ML
authors.lastname: Martino
authors.affiliation: Servicio de Hematología de Hospital General de Segovia.
authors.forename: José
authors.initials: J
authors.lastname: Hernández
authors.affiliation: Servicio de Hematología del Hospital Universitario de Salamanca, IBSAL IBMCC (USAL-CSIC), Salamanca.
authors.forename: Jesús María
authors.initials: JM
authors.lastname: Hernández-Rivas
authors.affiliation: Departamento de Química Física, Facultad de Farmacia, Universidad de Salamanca, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Burguillo
authors.affiliation: Servicio de Hematología del Hospital Universitario de Salamanca, IBSAL IBMCC (USAL-CSIC), Salamanca.
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.affiliation: Servicio de Hematología del Hospital Universitario de Salamanca, IBSAL IBMCC (USAL-CSIC), Salamanca.
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000175:diagnosis* / Q000235:genetics*