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

Martínez‐López, Joaquín; Corchete, Luis A.; Sánchez-Vega, Beatriz; Rapado, Inmaculada; Puig, Noemí; Barrio, Santiago; Sánchez, María Luz; Alignani, Diego; Lasa, Marta; Coca, Alfonso García de; Pardal, Emilia; Oriol, Albert; Garcia, Maria-Esther Gonzalez; Escalante, Fernando; González-López, Tomás José; Palomera, Luis; Alonso, José M.; Prósper, Felipe; Órfão, Alberto; Vidriales, María‐Belén; Mateos, María Victoria; Lahuerta, Juan José; Gutiérrez, Norma C.; Miguel, Jesús F. San

doi:10.1182/blood-2015-10-673095

Cited by 35 publications

(35 citation statements)

References 25 publications

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“…Compared to our study, work published by the Spanish group [4] analyzed 11 ALA patients and identified lower number of single nucleotide polymorphisms (SNVs) per patient (median 15 vs. 64 SNVs) (Graph 1). The discrepancy could be caused by differences in library preparation, sequencing protocol/ platform and/ or mutation calling algorithm.…”

Section: Genome Levelcontrasting

confidence: 54%

“…Although, knowledge about MM PC biology and pathology increased significantly in the last decade, the same cannot be said about ALA. Until this time only two studies were focused on description of genomic landscape of ALA using next generation sequencing [4] or/ and array comparative genome hybridization (CGH) [4,5].…”

Section: Genome Levelmentioning

confidence: 99%

“…In addition, the study of Paiva et al [4] included high throughput genetic profiling of purified clonal PCs from the ALA patients. Copy number alterations (CNA) were detected in all tested samples with median 9 CNA per patient version 1.3.1), with minor modifications based on our previous experience.…”

Section: Genome Levelmentioning

confidence: 99%

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Biomarkers in Immunoglobulin Light Chain Amyloidosis

Kufova¹,

Ševčíková²,

Growková³

et al. 2017

Klin Onkol

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Immunoglobulin light chain amyloidosis (AL amyloidosis - ALA) is a monoclonal gammopathy characterized by presence of aberrant plasma cells producing amyloidogenic immunoglobulin light chains. This leads to formation of amyloid fibrils in various organs and tissues, mainly in heart and kidney, and causes their dysfunction. As amyloid depositing in target organs is irreversible, there is a big effort to identify biomarker that could help to distinguish ALA from other monoclonal gammopathies in the early stages of disease, when amyloid deposits are not fatal yet. High throughput technologies bring new opportunities to modern cancer research as they enable to study disease within its complexity. Sophisticated methods such as next generation sequencing, gene expression profiling and circulating microRNA profiling are new approaches to study aberrant plasma cells from patients with light chain amyloidosis and related diseases. While generally known mutation in multiple myeloma patients (KRAS, NRAS, MYC, TP53) were not found in ALA, number of mutated genes is comparable. Transcriptome of ALA patients proves to be more similar to monoclonal gammopathy of undetermined significance patients, moreover level of circulating microRNA, that are known to correlate with heart damage, is increased in ALA patients, where heart damage in ALA typical symptom.Key words: amyloidosis - plasma cell - genome - transcriptome - microRNA.

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Section: Genome Levelcontrasting

confidence: 54%

Section: Genome Levelmentioning

confidence: 99%

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Biomarkers in Immunoglobulin Light Chain Amyloidosis

Kufova¹,

Ševčíková²,

Growková³

et al. 2017

Klin Onkol

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“…A lower level of clonal plasma cells detected by MFC correlates with longer survival. 4 Studies on MFC utilization in AL amyloidosis are limited, [5][6][7][8][9][10][11] with only a few addressing the clinical relevance of MFC in this rare disorder. 11,12 Paiva et al reported MFC results in 35 patients with AL amyloidosis and found that the presence of .1% monotypic PCs in the bone marrow was associated with a shorter survival.…”

Section: Introductionmentioning

confidence: 99%

The prognostic value of multiparametric flow cytometry in AL amyloidosis at diagnosis and at the end of first-line treatment

Muchtar¹,

Jevremović²,

Dispenzieri³

et al. 2017

Blood

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Key Points• The monotypic and polytypic PC compartments assessed by MFC are prognostic in AL amyloidosis.• MFC may play a role in the definition of hematologic response to treatment.Multiparametric flow cytometry (MFC) in amyloid light-chain (AL) amyloidosis has not been widely adopted and, consequently, there is little information on its clinical relevance. We studied 173 patients with AL amyloidosis who underwent MFC immunophenotyping of bone marrow sample at diagnosis and 82 patients at the end of the first line of treatment (EOT). The number of monotypic plasma cells (PCs) and the polytypic PCs/bone marrow PCs (pPCs/BMPCs) ratio were analyzed. At diagnosis, ‡2.5% monotypic PCs was associated with a shorter progression-free survival (PFS) and overall survival (OS) compared with patients with <2.5% monotypic PCs (2-year PFS 41% vs 56%, P 5 .007; 2-year OS 55% vs 70%; P 5 .01). Additionally, patients with a pPCs/BMPCs ratio of £5% had a shorter PFS compared with patients with pPCs/BMPCs ratio >5% (2-year PFS 43% vs 55%; P 5 .02), but without OS difference (2-year OS 60% vs 67%; P 5 .19). In a multivariate analysis, the monotypic PCs retained an independent prediction for PFS/OS, whereas the pPCs/BMPCs ratio retained significance only for PFS. At EOT, ‡0.1% monotypic PCs was associated with a shorter PFS and OS compared with patients with <0.1% monotypic PCs (2-year PFS 31% vs 87%; P < .0001; 2-year OS 87% vs 98%, P 5 .02). In a subgroup analysis among patients who attained a very good partial response or better, the monotypic PCs at the 0.1% cutoff was predictive for progression rate but not for PFS/OS. MFC is prognostic for AL amyloidosis at diagnosis and at EOT. MFC may have a role in the definition of hematologic response. (Blood. 2017;129(1):82-87)

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“…Sequence-based analysis has come to play an integral role in many hematological malignancies [1], but disorders such as systemic light-chain (AL) amyloidosis remain poorly characterized due to its low incidence and small tumor size [2,3]. Thus, greater knowledge about the immunogenetic landscape of AL amyloidosis is required since, for example, potential differences between the genomic profiles of AL amyloidosis and multiple myeloma (MM) could help identifying patients with monoclonal gammopathies at greater risk of developing AL amyloidosis and monitor presymptomatic organ damage [4,5].…”

Section: To the Editormentioning

confidence: 99%

Immunogenetic characterization of clonal plasma cells in systemic light-chain amyloidosis

Cuenca¹,

Alameda

Sánchez-Vega³

et al. 2020

Leukemia

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

Abstract: Key Points Clonal PCs in AL have similar phenotypic and CNA profiles as those in MM, but their transcriptome is similar to that of normal PCs. First-ever WES in AL amyloidosis reveals potential lack of a unifying mutation.

Cited by 35 publications

References 25 publications

Biomarkers in Immunoglobulin Light Chain Amyloidosis

Biomarkers in Immunoglobulin Light Chain Amyloidosis

The prognostic value of multiparametric flow cytometry in AL amyloidosis at diagnosis and at the end of first-line treatment

Immunogenetic characterization of clonal plasma cells in systemic light-chain amyloidosis

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