English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/135727
Título

Phenotypic identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential

AutorPaíno, Teresa; Paiva, Bruno; Sayagués, José María; Corchete, Luis A.; Bárcena, Paloma; Ocio, Enrique M.; San-Segundo, Laura; Sarasquete, María Eugenia; García-Sanz, Ramón; Vidriales, Belén; Hernández, M. Teresa ; Paiva, Artur; Bladé, Joan; Lahuerta, Juan José; Orfao, Alberto; Mateos, Maria Victoria; Gutiérrez, Norma Carmen; San Miguel, Jesús F.
Fecha de publicación2015
CitaciónLeukemia 29(5): 1186-1194 (2015)
ResumenKnowledge about clonal diversity and selection is critical to understand multiple myeloma (MM) pathogenesis, chemoresistance and progression. If targeted therapy becomes reality, identification and monitoring of intraclonal plasma cell (PC) heterogeneity would become increasingly demanded. Here we investigated the kinetics of intraclonal heterogeneity among 116 MM patients using 23-marker multidimensional flow cytometry (MFC) and principal component analysis, at diagnosis and during minimal residual disease (MRD) monitoring. Distinct phenotypic subclones were observed in 35116 (30%) newly diagnosed MM patients. In 1035 patients, persistent MRD was detected after 9 induction cycles, and longitudinal comparison of patient-paired diagnostic vs MRD samples unraveled phenotypic clonal tiding after therapy in half (510) of the patients. After demonstrating selection of distinct phenotypic subsets by therapeutic pressure, we investigated whether distinct fluorescence-activated cell-sorted PC subclones had different clonogenic and cytogenetic profiles. In half (510) of the patients analyzed, distinct phenotypic subclones showed different clonogenic potential when co-cultured with stromal cells, and in 611 cases distinct phenotypic subclones displayed unique cytogenetic profiles by interphase fluorescence in situ hybridization, including selective del(17p13). Collectively, we unravel potential therapeutic selection of preexisting diagnostic phenotypic subclones during MRD monitoring; because phenotypically distinct PCs may show different clonogenic and cytogenetic profiles, identification and follow-up of unique phenotypic-genetic myeloma PC subclones may become relevant for tailored therapy.
URIhttp://hdl.handle.net/10261/135727
DOI10.1038/leu.2014.321
Identificadoresdoi: 10.1038/leu.2014.321
e-issn: 1476-5551
issn: 0887-6924
Aparece en las colecciones: (IBMCC) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.