Unknown,Transcriptomics,Genomics,Proteomics

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In vitro response to l-asparaginase in acute lymphoblastic leukemia

ABSTRACT: This SuperSeries is composed of the following subset Series: 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 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. Refer to individual Series

ORGANISM(S): Homo sapiens

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PROVIDER: E-GEOD-4397 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A genome-wide view of the in vitro response to l-asparaginase in acute lymphoblastic leukemia.

Fine Bernard M BM Kaspers Gertjan J L GJ Ho Minh M Loonen Anne H AH Boxer Linda M LM

Cancer research 20050101 1

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-asparaginas ...[more]

PMID: 15665306

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Dataset Information

In vitro response to l-asparaginase in acute lymphoblastic leukemia

Publications

A genome-wide view of the in vitro response to l-asparaginase in acute lymphoblastic leukemia.

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