GEO DataSets

(Submitter supplied) 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. This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS2494

Platform:

GPL96

38 Samples

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(Submitter supplied) 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

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS2493

Platform:

GPL96

29 Samples

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Analysis of pretreatment acute lymphoblastic leukemia samples that are either sensitive or resistant to glucocorticoid (GC)-induced apoptosis in vitro. Results used to search a database of expression profiles of pharmacologic treatment of cells for small molecules that reverse the resistance to GCs.

Organism:

Homo sapiens

Type:

Expression profiling by array, count, 2 disease state sets

Platform:

GPL96

Series:

GSE5820

29 Samples

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(Submitter supplied) Affymetrix submissions are typically submitted to GEO using the GEOarchive method described at http://www.ncbi.nlm.nih.gov/projects/geo/info/geo_affy.html June 03, 2009: annotation table updated with netaffx build 28 June 08, 2012: annotation table updated with netaffx build 32 June 24, 2016: annotation table updated with netaffx build 35 Protocol: see manufacturer's web site The U133 set includes 2 arrays with a total of 44928 entries and was indexed 29-Jan-2002. more...

Organism:

Homo sapiens

364 DataSets

1125 Series

11 Related Platforms

42429 Samples

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