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Series GSE95809 Query DataSets for GSE95809
Status Public on Feb 14, 2018
Title Modulation of Navitoclax Sensitivity by Dihydroarteminisin-Mediated MCL-1 Repression
Organism Mus musculus
Experiment type Expression profiling by array
Summary Poor prognosis BCR-ABL+ B-ALL leukemic cells are highly dependent on the expression of endogenous anti-apoptotic MCL-1. However, the survival of most normal blood cells (e.g. progenitors, lymphocytes, and granulocytes) and other normal cell types (e.g. cardiomyocytes and neurons) are also exquisitely dependent on Mcl-1 gene expression, suggesting that effective therapeutic inhibition of MCL-1 could be acutely toxic, especially when combined with standard chemotherapy. Therefore, as an alternative to MCL-1 inhibition, we have identified dihydroarteminisin (DHA), a water-soluble metabolite of the anti-malarial arteminisin, which induces the down-modulation of MCL-1 protein expression by triggering an endoplasmic reticulum stress response. The DHA induced repression of MCL-1 expression renders leukemic cells highly sensitive to synergistic cell death induced by BH3-mimetic agents such as navitoclax (ABT-263) in a mouse model of BCR-ABL+ B-ALL. Furthermore, DHA also synergizes with navitoclax in human Ph+ ALL cell lines, and primary patient derived xenografts of Ph+ ALL. These data demonstrate that combining DHA with BH3-mimetic agents can improve therapeutic response in poor prognosis leukemia.
 
Overall design We used microarrays to compare the DHA treatement to controls in mice.
 
Contributor(s) Budhraja A, Tunis M, Churchman ML, Kothari AR, Yang X, Xu H, Kaminska E, Panetta JC, Finkelstein D, Opferman JT
Citation(s) 28974549
Submission date Mar 08, 2017
Last update date Feb 21, 2018
Contact name David Finkelstein
E-mail(s) david.finkelstein@stjude.org
Phone 9014953931
Organization name St Jude Children's Research Hospital
Department Computational Biology
Street address 332 N. Lauderdale St.
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (1)
GPL16570 [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]
Samples (6)
GSM2526321 DMSO control (con216)
GSM2526322 DMSO control (con226)
GSM2526323 DMSO control (con416)
Relations
BioProject PRJNA378488

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE95809_RAW.tar 55.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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