Identification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.

Chronic lymphocytic leukemia (CLL) is an adult lymphoid malignancy with a variable clinical course. There is considerable interest in the identification of new treatments, as most current approaches are not curative. While most patients respond to initial chemotherapy, relapsed disease is often resi...

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Autores principales:	Min Shen, Yaqin Zhang, Nakhle Saba, Christopher P Austin, Adrian Wiestner, Douglas S Auld
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ab0c08231de409980597047b5884657
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spelling	oai:doaj.org-article:9ab0c08231de409980597047b58846572021-11-18T08:54:21ZIdentification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.1932-620310.1371/journal.pone.0075252https://doaj.org/article/9ab0c08231de409980597047b58846572013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24073257/?tool=EBIhttps://doaj.org/toc/1932-6203Chronic lymphocytic leukemia (CLL) is an adult lymphoid malignancy with a variable clinical course. There is considerable interest in the identification of new treatments, as most current approaches are not curative. While most patients respond to initial chemotherapy, relapsed disease is often resistant to the drugs commonly used in CLL and patients are left with limited therapeutic options. In this study, we used a luminescent cell viability assay based on ATP levels to find compounds that were potent and efficacious in killing CLL cells. We employed an in-house process of quantitative high throughput screening (qHTS) to assess 8 concentrations of each member of a 2,816 compound library (including FDA-approved drugs and those known to be bio-active from commercial suppliers). Using qHTS we generated potency values on each compound in lymphocytes donated from each of six individuals with CLL and five unaffected individuals. We found 102 compounds efficacious against cells from all six individuals with CLL ("consensus" drugs) with five of these showing low or no activity on lymphocytes from a majority of normal donors, suggesting some degree of specificity for the leukemic cells. To our knowledge, this is the first study to screen a drug library against primary CLL cells to identify candidate agents for anti-cancer therapy. The results presented here offer possibilities for the development of novel drug candidates for therapeutic uses to treat CLL and other diseases.Min ShenYaqin ZhangNakhle SabaChristopher P AustinAdrian WiestnerDouglas S AuldPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e75252 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Min Shen Yaqin Zhang Nakhle Saba Christopher P Austin Adrian Wiestner Douglas S Auld Identification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.
description	Chronic lymphocytic leukemia (CLL) is an adult lymphoid malignancy with a variable clinical course. There is considerable interest in the identification of new treatments, as most current approaches are not curative. While most patients respond to initial chemotherapy, relapsed disease is often resistant to the drugs commonly used in CLL and patients are left with limited therapeutic options. In this study, we used a luminescent cell viability assay based on ATP levels to find compounds that were potent and efficacious in killing CLL cells. We employed an in-house process of quantitative high throughput screening (qHTS) to assess 8 concentrations of each member of a 2,816 compound library (including FDA-approved drugs and those known to be bio-active from commercial suppliers). Using qHTS we generated potency values on each compound in lymphocytes donated from each of six individuals with CLL and five unaffected individuals. We found 102 compounds efficacious against cells from all six individuals with CLL ("consensus" drugs) with five of these showing low or no activity on lymphocytes from a majority of normal donors, suggesting some degree of specificity for the leukemic cells. To our knowledge, this is the first study to screen a drug library against primary CLL cells to identify candidate agents for anti-cancer therapy. The results presented here offer possibilities for the development of novel drug candidates for therapeutic uses to treat CLL and other diseases.
format	article
author	Min Shen Yaqin Zhang Nakhle Saba Christopher P Austin Adrian Wiestner Douglas S Auld
author_facet	Min Shen Yaqin Zhang Nakhle Saba Christopher P Austin Adrian Wiestner Douglas S Auld
author_sort	Min Shen
title	Identification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.
title_short	Identification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.
title_full	Identification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.
title_fullStr	Identification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.
title_full_unstemmed	Identification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.
title_sort	identification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9ab0c08231de409980597047b5884657
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Identification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.

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