Portal de investigación
Differentiation stage of myeloma plasma cells: biological and clinical significance
Fecha de publicación:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Paiva B
- Puig N
- Cedena MT
- de Jong BG
- Ruiz Y
- Rapado I
- Martinez-Lopez J
- Alignani D
- Delgado JA
- van Zelm MC
- Van Dongen JJ
- Pascual M
- Agirre X
- Prosper F
- Martín-Subero JI
- Vidriales MB
- Gutierrez NC
- Hernandez MT
- Oriol A
- Echeveste MA
- Gonzalez Y
- Johnson SK
- Epstein J
- Barlogie B
- Morgan GJ
- Orfao A
- Blade J
- Mateos MV
- Lahuerta JJ
- San-Miguel JF
Grupos
Abstract
The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n = 20) that the CD19 - CD81 expression axis identifies three bone marrow (BM) PC subsets with distinct age- prevalence, proliferation, replication- history, immunoglobulin- production, and phenotype, consistent with progressively increased differentiation from CD19+ CD81+ into CD19 - CD81+ and CD19 - CD81 - BMPCs. Afterwards, we demonstrated in 225 newly diagnosed MM patients that, comparing to normal BMPC counterparts, 59% had fully differentiated (CD19 - CD81 -) clones, 38% intermediate- differentiated (CD19 - CD81+) and 3% less- differentiated (CD19+ CD81+) clones. The latter patients had dismal outcome, and PC differentiation emerged as an independent prognostic marker for progression- free (HR: 1.7; P = 0.005) and overall survival (HR: 2.1; P = 0.006). Longitudinal comparison of diagnostic vs minimal- residual- disease samples (n = 40) unraveled that in 20% of patients, less- differentiated PCs subclones become enriched after therapy- induced pressure. We also revealed that CD81 expression is epigenetically regulated, that less- differentiated clonal PCs retain high expression of genes related to preceding B- cell stages (for example: PAX5), and show distinct mutation profile vs fully differentiated PC clones within individual patients. Together, we shed new light into PC plasticity and demonstrated that MM patients harbouring less- differentiated PCs have dismal survival, which might be related to higher chemoresistant potential plus different molecular and genomic profiles.
Datos de la publicación
- ISSN/ISSNe:
- 0887-6924, 1476-5551
- Tipo:
- Article
- Páginas:
- 382-392
- DOI:
- 10.1038/leu.2016.211
- PubMed:
- 27479184
- Factor de Impacto:
- 5,131 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Leukemia NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 85
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