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Abstract: Knowledge 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 35/116 (30%) newly diagnosed MM patients. In 10/35 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 (5/10) 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 (5/10) of the patients analyzed, distinct phenotypic subclones showed different clonogenic potential when co-cultured with stromal cells, and in 6/11 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.
Fuente: Leukemia, 29(5), 1186-1194
Editorial: Nature Publishing Group
Año de publicación: 2015
Tipo de publicación: Artículo de Revista
DOI: 10.1038/leu.2014.321
ISSN: 0887-6924,1476-5551
Url de la publicación: https://doi.org/10.1038/leu.2014.321
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PAÍNO, TERESA
PAIVA, BRUNO
SAYAGUÉS, JOSÉ MARÍA
MOTA, INES
CARVALHEIRO, TIAGO
AIRES-MEJÍA, IRENE
PÉREZ, JOSÉ JUAN
SÁNCHEZ, MARIÁ LUZ
BÁRCENA, PALOMA
SAN-SEGUNDO, LAURA
ENRIQUE MARIA OCIO SAN MIGUEL
SARASQUETE, MARÍA EUGENIA
GARCÍA SANZ, RAMÓN
VIDRIALES, MARÍA BELÉN
ORIOL, ALBERT
HERNÁNDEZ, MIGUEL TEODORO
ECHEVESTE, MARÍA ASUNCIÓN
PAIVA, ARTUR AUGUSTO
BLADÉ, JOAN
LAHUERTA, JUAN JOSÉ
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