Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.

The bone marrow is a frequent location of primary relapse after conventional cytotoxic drug treatment of human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Because stromal cells have a major role in promoting chemotherapy resistance, they should be included to more realistically model in...

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Autores principales:	Annie Luong, Fabio Cerignoli, Yama Abassi, Nora Heisterkamp, Hisham Abdel-Azim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fb726bee2dec474d82344c0560cf0c59
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spelling	oai:doaj.org-article:fb726bee2dec474d82344c0560cf0c592021-12-02T20:13:53ZAnalysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.1932-620310.1371/journal.pone.0258140https://doaj.org/article/fb726bee2dec474d82344c0560cf0c592021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258140https://doaj.org/toc/1932-6203The bone marrow is a frequent location of primary relapse after conventional cytotoxic drug treatment of human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Because stromal cells have a major role in promoting chemotherapy resistance, they should be included to more realistically model in vitro drug treatment. Here we validated a novel application of the xCELLigence system as a continuous co-culture to assess long-term effects of drug treatment on BCP-ALL cells. We found that bone marrow OP9 stromal cells adhere to the electrodes but are progressively displaced by dividing patient-derived BCP-ALL cells, resulting in reduction of impedance over time. Death of BCP-ALL cells due to drug treatment results in re-adherence of the stromal cells to the electrodes, increasing impedance. Importantly, vincristine inhibited proliferation of sensitive BCP-ALL cells in a dose-dependent manner, correlating with increased impedance. This system was able to discriminate sensitivity of two relapsed Philadelphia chromosome (Ph) positive ALLs to four different targeted kinase inhibitors. Moreover, differences in sensitivity of two CRLF2-drivenBCP-ALL cell lines to ruxolitinib were also seen. These results show that impedance can be used as a novel approach to monitor drug treatment and sensitivity of primary BCP-ALL cells in the presence of protective microenvironmental cells.Annie LuongFabio CerignoliYama AbassiNora HeisterkampHisham Abdel-AzimPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0258140 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Annie Luong Fabio Cerignoli Yama Abassi Nora Heisterkamp Hisham Abdel-Azim Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.
description	The bone marrow is a frequent location of primary relapse after conventional cytotoxic drug treatment of human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Because stromal cells have a major role in promoting chemotherapy resistance, they should be included to more realistically model in vitro drug treatment. Here we validated a novel application of the xCELLigence system as a continuous co-culture to assess long-term effects of drug treatment on BCP-ALL cells. We found that bone marrow OP9 stromal cells adhere to the electrodes but are progressively displaced by dividing patient-derived BCP-ALL cells, resulting in reduction of impedance over time. Death of BCP-ALL cells due to drug treatment results in re-adherence of the stromal cells to the electrodes, increasing impedance. Importantly, vincristine inhibited proliferation of sensitive BCP-ALL cells in a dose-dependent manner, correlating with increased impedance. This system was able to discriminate sensitivity of two relapsed Philadelphia chromosome (Ph) positive ALLs to four different targeted kinase inhibitors. Moreover, differences in sensitivity of two CRLF2-drivenBCP-ALL cell lines to ruxolitinib were also seen. These results show that impedance can be used as a novel approach to monitor drug treatment and sensitivity of primary BCP-ALL cells in the presence of protective microenvironmental cells.
format	article
author	Annie Luong Fabio Cerignoli Yama Abassi Nora Heisterkamp Hisham Abdel-Azim
author_facet	Annie Luong Fabio Cerignoli Yama Abassi Nora Heisterkamp Hisham Abdel-Azim
author_sort	Annie Luong
title	Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.
title_short	Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.
title_full	Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.
title_fullStr	Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.
title_full_unstemmed	Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.
title_sort	analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/fb726bee2dec474d82344c0560cf0c59
work_keys_str_mv	AT annieluong analysisofacutelymphoblasticleukemiadrugsensitivitybychangesinimpedanceviastromalcelladherence AT fabiocerignoli analysisofacutelymphoblasticleukemiadrugsensitivitybychangesinimpedanceviastromalcelladherence AT yamaabassi analysisofacutelymphoblasticleukemiadrugsensitivitybychangesinimpedanceviastromalcelladherence AT noraheisterkamp analysisofacutelymphoblasticleukemiadrugsensitivitybychangesinimpedanceviastromalcelladherence AT hishamabdelazim analysisofacutelymphoblasticleukemiadrugsensitivitybychangesinimpedanceviastromalcelladherence
_version_	1718374742480650240

Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.

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