2026-09-14T13:09:17Zhttps://gredos.usal.es/oai/request
oai:gredos.usal.es:10366/1624732026-01-15T20:45:08Zcom_10366_4577com_10366_4576com_10366_3823col_10366_4578
Gestión del Repositorio Documental de la Universidad de Salamanca author Paíno Gómez, María Teresa author Paiva, B author Sayagués Manzano, José María author Mota, I author Carvalheiro, T author Corchete, L A author Aires-Mejía, I author Pérez, J J author Sanchez García , María author Barcena, P author Ocio, E M author San-Segundo, L author Sarasquete, M E author García Sanz, Ramón author Vidriales Vicente, María Belén author Oriol, A author Hernández, M-T author Echeveste, M-A author Paiva, A author Blade, J author Lahuerta, J-J author Orfao de Matos Correia e Vale, José Alberto author Mateos Manteca, María Victoria author Gutiérrez, N C author San-Miguel, J F 2025-01-27T08:59:21Z 2025-01-27T08:59:21Z 2014 Paíno, T., Paiva, B., Sayagués, J. M., Mota, I., Carvalheiro, T., Corchete, L. A., ... & San-Miguel, J. F. (2015). Phenotypic identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential. Leukemia, 29(5), 1186-1194. 0887-6924 http://hdl.handle.net/10366/162473 10.1038/leu.2014.321 25388955 1476-5551 [EN]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. eng Attribution-NonCommercial-NoDerivatives 4.0 Internacional myeloma Plasma cells Flow cytometry Clonal heterogeneity Treatment pressure Phenotypic identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential info:eu-repo/semantics/article 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 URL https://gredos.usal.es/bitstream/10366/162473/1/Pa%c3%adno_Leukemia.pdf File MD5 4069362a5b6eb001eebae520dc521e2b 1173290 application/pdf Paíno_Leukemia.pdf URL https://gredos.usal.es/bitstream/10366/162473/4/Pa%c3%adno_Leukemia.pdf.txt File MD5 afc44d5fc126b67be0f1b1c3b7bb114e 43571 text/plain Paíno_Leukemia.pdf.txt