title: Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis.
abstract: Immunoglobulin light-chain amyloidosis (AL) and multiple myeloma (MM) are 2 distinct monoclonal gammopathies that involve the same cellular compartment: clonal plasma cells (PCs). Despite the fact that knowledge about MM PC biology has significantly increased in the last decade, the same does not apply for AL. Here, we used an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 24 newly diagnosed patients with AL. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and both monoclonal gammopathy of undetermined significance and MM PCs. However, in contrast to MM, highly purified fluorescence-activated cell-sorted clonal PCs from AL (n = 9) showed almost normal transcriptome, with only 38 deregulated genes vs normal PCs; these included a few tumor-suppressor (CDH1, RCAN) and proapoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n = 11) were genomically unstable, with a median of 9 copy number alterations (CNAs) per case, many of such CNAs being similar to those found in MM. Whole-exome sequencing (WES) performed in 5 AL patients revealed a median of 15 nonrecurrent mutations per case. Altogether, our results show that in the absence of a unifying mutation by WES, clonal PCs in AL display phenotypic and CNA profiles similar to MM, but their transcriptome is remarkably similar to that of normal PCs.
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain;
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Hospital 12 de Octubre, Madrid, Spain;
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martinez-Lopez
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC CSIC-USAL), Salamanca, Spain;
authors.forename: Luis A
authors.initials: LA
authors.lastname: Corchete
authors.affiliation: Hospital 12 de Octubre, Madrid, Spain;
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sanchez-Vega
authors.affiliation: Hospital 12 de Octubre, Madrid, Spain;
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Rapado
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC CSIC-USAL), Salamanca, Spain;
authors.forename: Noemi
authors.initials: N
authors.lastname: Puig
authors.affiliation: Hospital 12 de Octubre, Madrid, Spain;
authors.forename: Santiago
authors.initials: S
authors.lastname: Barrio
authors.affiliation: Servicio General de Citometría and Department of Medicine, IBSAL, and IBMCC CSIC-USAL, Salamanca, Universidad de Salamanca, Salamanca, Spain;
authors.forename: Maria-Luz
authors.initials: ML
authors.lastname: Sanchez
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain;
authors.forename: Diego
authors.initials: D
authors.lastname: Alignani
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain;
authors.forename: Marta
authors.initials: M
authors.lastname: Lasa
authors.affiliation: Hospital Clínico Universitario de Valladolid, Valladolid, Spain;
authors.forename: Alfonso
authors.initials: A
authors.lastname: García de Coca
authors.affiliation: Hospital Virgen del Puerto, Plasencia, Spain;
authors.forename: Emilia
authors.initials: E
authors.lastname: Pardal
authors.affiliation: Hospital German Trias i Pujol, Badalona, Spain;
authors.forename: Alberto
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Hospital de Cabueñes, Gijón, Spain;
authors.forename: Maria-Esther Gonzalez
authors.initials: ME
authors.lastname: Garcia
authors.affiliation: Complejo Hospitalario de León, León, Spain;
authors.forename: Fernando
authors.initials: F
authors.lastname: Escalante
authors.affiliation: Hospital Universitario de Burgos, Burgos, Spain;
authors.forename: Tomás J
authors.initials: TJ
authors.lastname: González-López
authors.affiliation: Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain; and.
authors.forename: Luis
authors.initials: L
authors.lastname: Palomera
authors.affiliation: Hospital Rio Carrión, Palencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Alonso
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain;
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
authors.affiliation: Servicio General de Citometría and Department of Medicine, IBSAL, and IBMCC CSIC-USAL, Salamanca, Universidad de Salamanca, Salamanca, Spain;
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC CSIC-USAL), Salamanca, Spain;
authors.forename: Maria-Belen
authors.initials: MB
authors.lastname: Vidriales
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC CSIC-USAL), Salamanca, Spain;
authors.forename: María-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Hospital 12 de Octubre, Madrid, Spain;
authors.forename: Juan-Jose
authors.initials: JJ
authors.lastname: Lahuerta
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC CSIC-USAL), Salamanca, Spain;
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutierrez
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain;
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000686:Amyloidosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D016130:Immunophenotyping; D046228:Microarray Analysis; D010265:Paraproteinemias / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome
chemical_list: D007147:Immunoglobulin Light Chains