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Series GSE5820 Query DataSets for GSE5820
Status Public on Sep 14, 2006
Title Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL-1 and glucocorticoid resistance
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Drug resistance remains a major obstacle to successful cancer treatment. Here we use a novel approach to identify rapamycin as a glucocorticoid resistance reversal agent. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in Acute Lymphoblastic Leukemia (ALL) cells. The screen indicated the mTOR inhibitor rapamycin profile matched the signature of GC-sensitivity. We thus tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells, and found that it sensitized cells to glucocorticoid induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis, and that the combination of rapamycin and glucocorticoids has potential utility in ALL. Furthermore this approach represents a novel strategy for identification of promising combination therapies for cancer.
Keywords: drug resistance comparison
Overall design primary acute lymphoblastic leukemia samples were determined to be sensitive or resistant to in vitro treatment with glucocorticoids. Samples were then hybrized to affymetrix microarrays
Citation(s) 17010674
Submission date Sep 13, 2006
Last update date Aug 10, 2018
Contact name Scott A. Armstrong
Phone 617-919-2508
Fax 617-730-0934
Organization name Children's Hospital
Department Hematology/Oncology
Street address 1 Blackfan Circle
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
Samples (29)
GSM135892 sensitive sample 1
GSM135893 Sensitive sample 2
GSM135894 sensitive sample 3
This SubSeries is part of SuperSeries:
GSE5824 Identification of rapamycin as a glucocorticoid resistance reversal agent
BioProject PRJNA104383

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