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

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

Autoría

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

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