Detalle Publicación


Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance

Autores: Paiva, Bruno; Corchete LA; Vidriales MB; Puig N; Maiso Castellanos, Patricia; Rodriguez I; Alignani D; Burgos Rodríguez, Leire; Sanchez ML; Barcena P; Echeveste MA; Hernandez MT; García-Sanz R; Ocio EM; Oriol A; Gironella M; Palomera L; De Arriba F; Gonzalez Y; Johnson SK; Epstein J; Barlogie B; Lahuerta JJ; Blade J; Orfao A; Mateos MV; San Miguel Izquierdo, Jesús; Grupo Español de Mieloma/Programa para el Estudio
Título de la revista: BLOOD
ISSN: 0006-4971
Volumen: 127
Número: 15
Páginas: 1896-1906
Fecha de publicación: 2016
Persistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) is associated with inferior survival in multiple myeloma (MM). Thus, characterization of the minor MRD subclone may represent a unique model to understand chemoresistance, but to our knowledge, the phenotypic and genetic features of the MRD subclone have never been investigated. Here, we compared the antigenic profile of MRD vs diagnostic clonal PCs in 40 elderly MM patients enrolled in the GEM2010MAS65 study and showed that the MRD subclone is enriched in cells overexpressing integrins (CD11a/CD11c/CD29/CD49d/CD49e), chemokine receptors (CXCR4), and adhesion molecules (CD44/CD54). Genetic profiling of MRD vs diagnostic PCs was performed in 12 patients; 3 of them showed identical copy number alterations (CNAs), in another 3 cases, MRD clonal PCs displayed all genetic alterations detected at diagnosis plus additional CNAs that emerged at the MRD stage, whereas in the remaining 6 patients, there were CNAs present at diagnosis that were undetectable in MRD clonal PCs, but also a selected number of genetic alterations that became apparent only at the MRD stage. The MRD subclone showed significant downregulation of genes related to protein processing in endoplasmic reticulum, as well as novel deregulated genes such asALCAMthat is prognostically relevant in MM and may identify chemoresistant PCs in vitro. Altogether, our results suggest that therapy-induced clonal selection could be already present at t