Targeted therapy of human leukemia xenografts in immunodeficient zebrafish

Abstract Personalized medicine holds tremendous promise for improving safety and efficacy of drug therapies by optimizing treatment regimens. Rapidly developed patient-derived xenografts (pdx) could be a helpful tool for analyzing the effect of drugs against an individual’s tumor by growing the tumo...

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Autores principales:	Ranganatha R. Somasagara, Xiaoyan Huang, Chunyu Xu, Jamil Haider, Jonathan S. Serody, Paul M. Armistead, TinChung Leung
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ca05924fb6f54487b4ff2e4948c6d8d3
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spelling	oai:doaj.org-article:ca05924fb6f54487b4ff2e4948c6d8d32021-12-02T11:35:59ZTargeted therapy of human leukemia xenografts in immunodeficient zebrafish10.1038/s41598-021-85141-52045-2322https://doaj.org/article/ca05924fb6f54487b4ff2e4948c6d8d32021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85141-5https://doaj.org/toc/2045-2322Abstract Personalized medicine holds tremendous promise for improving safety and efficacy of drug therapies by optimizing treatment regimens. Rapidly developed patient-derived xenografts (pdx) could be a helpful tool for analyzing the effect of drugs against an individual’s tumor by growing the tumor in an immunodeficient animal. Severe combined immunodeficiency (SCID) mice enable efficient in vivo expansion of vital tumor cells and generation of personalized xenografts. However, they are not amenable to large-scale rapid screening, which is critical in identifying new compounds from large compound libraries. The development of a zebrafish model suitable for pdx could facilitate large-scale screening of drugs targeted against specific malignancies. Here, we describe a novel strategy for establishing a zebrafish model for drug testing in leukemia xenografts. We used chronic myelogenous leukemia and acute myeloid leukemia for xenotransplantation into SCID zebrafish to evaluate drug screening protocols. We showed the in vivo efficacy of the ABL inhibitor imatinib, MEK inhibitor U0126, cytarabine, azacitidine and arsenic trioxide. We performed corresponding in vitro studies, demonstrating that combination of MEK- and FLT3-inhibitors exhibit an enhanced effect in vitro. We further evaluated the feasibility of zebrafish for transplantation of primary human hematopoietic cells that can survive at 15 day-post-fertilization. Our results provide critical insights to guide development of high-throughput platforms for evaluating leukemia.Ranganatha R. SomasagaraXiaoyan HuangChunyu XuJamil HaiderJonathan S. SerodyPaul M. ArmisteadTinChung LeungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ranganatha R. Somasagara Xiaoyan Huang Chunyu Xu Jamil Haider Jonathan S. Serody Paul M. Armistead TinChung Leung Targeted therapy of human leukemia xenografts in immunodeficient zebrafish
description	Abstract Personalized medicine holds tremendous promise for improving safety and efficacy of drug therapies by optimizing treatment regimens. Rapidly developed patient-derived xenografts (pdx) could be a helpful tool for analyzing the effect of drugs against an individual’s tumor by growing the tumor in an immunodeficient animal. Severe combined immunodeficiency (SCID) mice enable efficient in vivo expansion of vital tumor cells and generation of personalized xenografts. However, they are not amenable to large-scale rapid screening, which is critical in identifying new compounds from large compound libraries. The development of a zebrafish model suitable for pdx could facilitate large-scale screening of drugs targeted against specific malignancies. Here, we describe a novel strategy for establishing a zebrafish model for drug testing in leukemia xenografts. We used chronic myelogenous leukemia and acute myeloid leukemia for xenotransplantation into SCID zebrafish to evaluate drug screening protocols. We showed the in vivo efficacy of the ABL inhibitor imatinib, MEK inhibitor U0126, cytarabine, azacitidine and arsenic trioxide. We performed corresponding in vitro studies, demonstrating that combination of MEK- and FLT3-inhibitors exhibit an enhanced effect in vitro. We further evaluated the feasibility of zebrafish for transplantation of primary human hematopoietic cells that can survive at 15 day-post-fertilization. Our results provide critical insights to guide development of high-throughput platforms for evaluating leukemia.
format	article
author	Ranganatha R. Somasagara Xiaoyan Huang Chunyu Xu Jamil Haider Jonathan S. Serody Paul M. Armistead TinChung Leung
author_facet	Ranganatha R. Somasagara Xiaoyan Huang Chunyu Xu Jamil Haider Jonathan S. Serody Paul M. Armistead TinChung Leung
author_sort	Ranganatha R. Somasagara
title	Targeted therapy of human leukemia xenografts in immunodeficient zebrafish
title_short	Targeted therapy of human leukemia xenografts in immunodeficient zebrafish
title_full	Targeted therapy of human leukemia xenografts in immunodeficient zebrafish
title_fullStr	Targeted therapy of human leukemia xenografts in immunodeficient zebrafish
title_full_unstemmed	Targeted therapy of human leukemia xenografts in immunodeficient zebrafish
title_sort	targeted therapy of human leukemia xenografts in immunodeficient zebrafish
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ca05924fb6f54487b4ff2e4948c6d8d3
work_keys_str_mv	AT ranganatharsomasagara targetedtherapyofhumanleukemiaxenograftsinimmunodeficientzebrafish AT xiaoyanhuang targetedtherapyofhumanleukemiaxenograftsinimmunodeficientzebrafish AT chunyuxu targetedtherapyofhumanleukemiaxenograftsinimmunodeficientzebrafish AT jamilhaider targetedtherapyofhumanleukemiaxenograftsinimmunodeficientzebrafish AT jonathansserody targetedtherapyofhumanleukemiaxenograftsinimmunodeficientzebrafish AT paulmarmistead targetedtherapyofhumanleukemiaxenograftsinimmunodeficientzebrafish AT tinchungleung targetedtherapyofhumanleukemiaxenograftsinimmunodeficientzebrafish
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Targeted therapy of human leukemia xenografts in immunodeficient zebrafish

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