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| Status |
Public on Mar 08, 2006 |
| Title |
In vitro response to l-asparaginase in acute lymphoblastic leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Abstract: To investigate the effect of l-asparaginase on acute lymphoblastic leukemia (ALL), we used cDNA microarrays to obtain a genome-wide view of gene expression both at baseline and after in vitro exposure to l-asparaginase in cell lines and pediatric ALL samples. In 16 cell lines, a baseline gene expression pattern distinguished l-asparaginase sensitivity from resistance. However, for 28 pediatric ALL samples, no consistent baseline expression pattern was associated with sensitivity to l-asparaginase. In particular, baseline expression of asparagine synthetase (ASNS) was not predictive of response to l-asparaginase. After exposure to l-asparaginase, 5 cell lines and 10 clinical samples exhibited very similar changes in the expression of a large number of genes. However, the gene expression changes occurred more slowly in the clinical samples. These changes included a consistent increase in expression of tRNA synthetases and solute transporters and activating transcription factor and CCAAT/enhancer binding protein family members, a response similar to that observed with amino acid starvation. There was also a consistent decrease in many genes associated with proliferation. Taken together, the changes seem to reflect a consistent coordinated response to asparagine starvation in both cell lines and clinical samples. Importantly, in the clinical samples, increased expression of ASNS after l-asparaginase exposure was not associated with in vitro resistance to l-asparaginase, indicating that ASNS-independent mechanisms of in vitro l-asparaginase resistance are common in ALL. These results suggest that targeting particular genes involved in the response to amino acid starvation in ALL cells may provide a novel way to overcome l-asparaginase resistance.
This SuperSeries is composed of the SubSeries listed below.
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| |
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| Overall design |
Refer to individual Series
|
| |
|
| Citation(s) |
15665306 |
| |
| Submission date |
Mar 07, 2006 |
| Last update date |
Dec 28, 2012 |
| Organization |
Stanford Microarray Database (SMD) |
| E-mail(s) |
array@genome.stanford.edu
|
| Phone |
650-498-6012
|
| URL |
http://genome-www5.stanford.edu/
|
| Department |
Stanford University, School of Medicine
|
| Street address |
300 Pasteur Drive
|
| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
|
| Platforms (5)
|
|
| Samples (109)
|
|
| This SuperSeries is composed of the following SubSeries: |
| GSE4070 |
Clinical acute lymphoblastic leukemia samples (untreated) with known asparaginase LC50 values |
| GSE4071 |
Clinical pediatric acute lymphoblastic leukemia samples after in vitro exposure to L-asparaginase |
| GSE4072 |
L-asparaginase exposure in acute lymphoblastic leukemia cell lines time series |
|
| Relations |
| BioProject |
PRJNA94591 |
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