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Title

Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis

AuthorsPaiva, Bruno; Martínez-López, Joaquín; Corchete, Luis A.; Sanchez-Vega, Beatriz; Rapado, Inmaculada; Puig, Noemi; Barrio, Santiago; Sánchez, Maria Luz; Alignani, Diego; Lasa, Marta; García de Coca, Alfonso; Pardal, Emilia; Oriol, Albert; Gonzalez Garcia, Maria-Esther; Escalante, Fernando; González-López, Tomás J.; Palomera, Luis; Alonso, Jose M.; Prosper, Felipe; Orfao, Alberto ; Vidriales, Maria Belén; Mateos, Maria Victoria; Lahuerta, Juan José; Gutiérrez, Norma Carmen; San Miguel, Jesús F.
Issue Date2016
PublisherAmerican Society of Hematology
CitationBlood 127: 3035- 3039 (2016)
AbstractImmunoglobulin 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.
URIhttp://hdl.handle.net/10261/168669
Identifiersdoi: 10.1182/blood-2015-10-673095
issn: 1528-0020
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