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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-05

AUTHORS

T Paíno, B Paiva, J M Sayagués, I Mota, T Carvalheiro, L A Corchete, I Aires-Mejía, J J Pérez, M L Sanchez, P Barcena, E M Ocio, L San-Segundo, M E Sarasquete, R García-Sanz, M-B Vidriales, A Oriol, M-T Hernández, M-A Echeveste, A Paiva, J Blade, J-J Lahuerta, A Orfao, M-V Mateos, N C Gutiérrez, J F San-Miguel

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. More... »

PAGES

1186

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/leu.2014.321

    DOI

    http://dx.doi.org/10.1038/leu.2014.321

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010343656

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25388955


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    435 https://www.grid.ac/institutes/grid.414651.3 schema:alternateName Donostia Unibertsitate Ospitalea
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