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Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation

Multiple myeloma (MM) has benefited from significant advancements in treatment that have improved outcomes and reduced morbidity. However, the disease remains incurable and is characterized by high rates of drug resistance and relapse. Consequently, methods to select the most efficacious therapy are...

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Autores principales: Cetin, Arif E., Stevens, Mark M., Calistri, Nicholas L., Fulciniti, Mariateresa, Olcum, Selim, Kimmerling, Robert J., Munshi, Nikhil C., Manalis, Scott R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694762/
https://www.ncbi.nlm.nih.gov/pubmed/29151572
http://dx.doi.org/10.1038/s41467-017-01593-2
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author Cetin, Arif E.
Stevens, Mark M.
Calistri, Nicholas L.
Fulciniti, Mariateresa
Olcum, Selim
Kimmerling, Robert J.
Munshi, Nikhil C.
Manalis, Scott R.
author_facet Cetin, Arif E.
Stevens, Mark M.
Calistri, Nicholas L.
Fulciniti, Mariateresa
Olcum, Selim
Kimmerling, Robert J.
Munshi, Nikhil C.
Manalis, Scott R.
author_sort Cetin, Arif E.
collection PubMed
description Multiple myeloma (MM) has benefited from significant advancements in treatment that have improved outcomes and reduced morbidity. However, the disease remains incurable and is characterized by high rates of drug resistance and relapse. Consequently, methods to select the most efficacious therapy are of great interest. Here we utilize a functional assay to assess the ex vivo drug sensitivity of single multiple myeloma cells based on measuring their mass accumulation rate (MAR). We show that MAR accurately and rapidly defines therapeutic susceptibility across human multiple myeloma cell lines to a gamut of standard-of-care therapies. Finally, we demonstrate that our MAR assay, without the need for extended culture ex vivo, correctly defines the response of nine patients to standard-of-care drugs according to their clinical diagnoses. This data highlights the MAR assay in both research and clinical applications as a promising tool for predicting therapeutic response using clinical samples.
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spelling pubmed-56947622017-11-22 Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation Cetin, Arif E. Stevens, Mark M. Calistri, Nicholas L. Fulciniti, Mariateresa Olcum, Selim Kimmerling, Robert J. Munshi, Nikhil C. Manalis, Scott R. Nat Commun Article Multiple myeloma (MM) has benefited from significant advancements in treatment that have improved outcomes and reduced morbidity. However, the disease remains incurable and is characterized by high rates of drug resistance and relapse. Consequently, methods to select the most efficacious therapy are of great interest. Here we utilize a functional assay to assess the ex vivo drug sensitivity of single multiple myeloma cells based on measuring their mass accumulation rate (MAR). We show that MAR accurately and rapidly defines therapeutic susceptibility across human multiple myeloma cell lines to a gamut of standard-of-care therapies. Finally, we demonstrate that our MAR assay, without the need for extended culture ex vivo, correctly defines the response of nine patients to standard-of-care drugs according to their clinical diagnoses. This data highlights the MAR assay in both research and clinical applications as a promising tool for predicting therapeutic response using clinical samples. Nature Publishing Group UK 2017-11-20 /pmc/articles/PMC5694762/ /pubmed/29151572 http://dx.doi.org/10.1038/s41467-017-01593-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Cetin, Arif E.
Stevens, Mark M.
Calistri, Nicholas L.
Fulciniti, Mariateresa
Olcum, Selim
Kimmerling, Robert J.
Munshi, Nikhil C.
Manalis, Scott R.
Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation
title Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation
title_full Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation
title_fullStr Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation
title_full_unstemmed Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation
title_short Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation
title_sort determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694762/
https://www.ncbi.nlm.nih.gov/pubmed/29151572
http://dx.doi.org/10.1038/s41467-017-01593-2
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