Effective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models.

2.50
Hdl Handle:
http://hdl.handle.net/2436/620216
Title:
Effective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models.
Authors:
Deng, Manman; Jiang, Zhiwu; Li, Yin; Zhou, Yong; Li, Jie; Wang, Xiangmeng; Yao, Yao; Wang, Weiguang; Li, Peng; Xu, Bing
Abstract:
Disulfiram (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.
Citation:
Effective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models. 2016 Oncotarget
Publisher:
Impact
Journal:
Oncotarget
Issue Date:
17-May-2016
URI:
http://hdl.handle.net/2436/620216
DOI:
10.18632/oncotarget.9413
PubMed ID:
27203215
Type:
Article
Language:
en
ISSN:
1949-2553
Appears in Collections:
Molecular Pharmacology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorDeng, Manmanen
dc.contributor.authorJiang, Zhiwuen
dc.contributor.authorLi, Yinen
dc.contributor.authorZhou, Yongen
dc.contributor.authorLi, Jieen
dc.contributor.authorWang, Xiangmengen
dc.contributor.authorYao, Yaoen
dc.contributor.authorWang, Weiguangen
dc.contributor.authorLi, Pengen
dc.contributor.authorXu, Bingen
dc.date.accessioned2016-10-17T15:27:36Z-
dc.date.available2016-10-17T15:27:36Z-
dc.date.issued2016-05-17-
dc.identifier.citationEffective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models. 2016 Oncotargeten
dc.identifier.issn1949-2553-
dc.identifier.pmid27203215-
dc.identifier.doi10.18632/oncotarget.9413-
dc.identifier.urihttp://hdl.handle.net/2436/620216-
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.en
dc.languageENG-
dc.language.isoenen
dc.publisherImpacten
dc.rightsArchived with thanks to Oncotargeten
dc.subjectadult B-cell acute lymphoblastic leukemiaen
dc.subjectcopperen
dc.subjectdisulfiramen
dc.subjectp16 deletionen
dc.subjectpatient-derived xenograften
dc.titleEffective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models.en
dc.typeArticleen
dc.identifier.journalOncotargeten

Related articles on PubMed

All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.