Scientific publications
Phenotypic, transcriptomic and genomic features of clonal plasma cells in light chain amyloidosis
Paiva B (1), Martinez-Lopez J (2), Corchete LA (3), Sanchez-Vega B (2), Rapado I (2), Puig N (3), Barrio S (2), Sanchez ML (4), Alignani D (5), Lasa M (5), García de Coca A (6), Pardal E (7), Oriol A (8), Gonzalez Garcia ME (9), Escalante F (10), González-López TJ (11), Palomera L (12), Alonso J (13), Prosper F (5), Orfao A (14), Vidriales MB (3), Mateos MV (3), Lahuerta JJ (2), Gutierrez NC (3), San Miguel JF (5).
ABSTRACT
Immunoglobulin light-chain amyloidosis (AL) and multiple myeloma (MM) are two distinct monoclonal gammopathies that involve the same cellular compartment: clonal plasma cells (PCs). Despite knowledge about MM PC biology has significantly increased in the last decade, the same does not apply to AL.
Here, we used an integrative phenotypic, molecular and genomic approach to study clonal PCs from 24 newly-diagnosed AL patients. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and both MGUS and MM PCs.
However, in contrast to MM, highly-purified FACS-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 pro-apoptotic (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 CNA being similar to those found in MM.
Whole-exome sequencing (WES) performed in five AL patients revealed a median of 15 non-recurrent 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.
CITATION Blood. 2016 Apr 11. pii: blood-2015-10-673095.
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