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dc.contributor.authorDeng, Manman
dc.contributor.authorJiang, Zhiwu
dc.contributor.authorLi, Yin
dc.contributor.authorZhou, Yong
dc.contributor.authorLi, Jie
dc.contributor.authorWang, Xiangmeng
dc.contributor.authorYao, Yao
dc.contributor.authorWang, Weiguang
dc.contributor.authorLi, Peng
dc.contributor.authorXu, Bing
dc.date.accessioned2017-02-21T14:56:33Z
dc.date.available2017-02-21T14:56:33Z
dc.date.issued2016-05-17
dc.identifier.citationDeng, M., Jiang, Z., Li, Y., Zhou, Y., Li, J., Wang, X., Yao, Y., Wang, W., Li, P., and Xu, B. (2016) Effective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models, Oncotarget, 2016; 7, pp. 82200-82212. https://doi.org/10.18632/oncotarget.9413
dc.identifier.issn1949-2553
dc.identifier.doi10.18632/oncotarget.9413
dc.identifier.urihttp://hdl.handle.net/2436/620385
dc.description.abstractDisulfiram (DS), a clinically used drug to control alcoholism, has displayed promising anti-cancer activity against a wide range of tumors. Here, we demonstrated that DS/copper (Cu) complex effectively eliminated adult B-ALL cells in vitro and in vivo in patient-derived xenograft (PDX) humanized mouse models, reflected by inhibition of cell proliferation, induction of apoptosis, suppression of colony formation, and reduction of PDX tumor growth, while sparing normal peripheral blood mononuclear cells. Mechanistically, these events were associated with disruption of mitochondrial membrane potential and down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL. Further analysis on B-ALL patients’ clinical characteristics revealed that the ex vivo efficacy of DS/Cu in primary samples was significantly correlated to p16 gene deletion and peripheral blood WBC counts at diagnosis, while age, LDH level, extramedullary infiltration, status post intensive induction therapy, immune phenotype, risk category, and Ph chromosome had no effect. Together, these findings indicate that disulfiram, particularly when administrated in combination with copper, might represent a potential repurposing agent for treatment of adult B-ALL patients, including those clinically characterized by one or more adverse prognostic factors.
dc.language.isoen
dc.publisherElsevier
dc.relation.urlhttp://www.oncotarget.com/abstract/9413
dc.subjectdisulfiram
dc.subjectcopper
dc.subjectadult B-cell acute lymphoblastic leukemia,
dc.subjectpatient-derived xenograft
dc.titleEffective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models
dc.typeJournal article
dc.identifier.journalOncotarget
dc.date.accepted2016-04-28
rioxxterms.funderUniversity of Wolverhampton
rioxxterms.identifier.projectUoW210217WW
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2017-02-21
refterms.dateFCD2018-10-19T09:24:44Z
refterms.versionFCDVoR
refterms.dateFOA2017-02-21T00:00:00Z
html.description.abstractDisulfiram (DS), a clinically used drug to control alcoholism, has displayed promising anti-cancer activity against a wide range of tumors. Here, we demonstrated that DS/copper (Cu) complex effectively eliminated adult B-ALL cells in vitro and in vivo in patient-derived xenograft (PDX) humanized mouse models, reflected by inhibition of cell proliferation, induction of apoptosis, suppression of colony formation, and reduction of PDX tumor growth, while sparing normal peripheral blood mononuclear cells. Mechanistically, these events were associated with disruption of mitochondrial membrane potential and down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL. Further analysis on B-ALL patients’ clinical characteristics revealed that the ex vivo efficacy of DS/Cu in primary samples was significantly correlated to p16 gene deletion and peripheral blood WBC counts at diagnosis, while age, LDH level, extramedullary infiltration, status post intensive induction therapy, immune phenotype, risk category, and Ph chromosome had no effect. Together, these findings indicate that disulfiram, particularly when administrated in combination with copper, might represent a potential repurposing agent for treatment of adult B-ALL patients, including those clinically characterized by one or more adverse prognostic factors.


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