Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA104899 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Time series of in vitro 2 IU/ml L-asparaginase exposure in acute lymphoblastic leukemia cell lines. Groups of assays that are related as part of a time series. Keywords: time_series_design
2006-01-21 | GSE4072 | GEO
Project description:Time series of in vitro 2 IU/ml L-asparaginase exposure in acute lymphoblastic leukemia cell lines.
2005-10-19 | E-SMDB-27 | biostudies-arrayexpress
Project description:Time series of in vitro 2 IU/ml L-asparaginase exposure in acute lymphoblastic leukemia cell lines.
2005-11-11 | E-SMDB-2978 | biostudies-arrayexpress
Project description:Time series of in vitro 2 IU/ml L-asparaginase exposure in acute lymphoblastic leukemia cell lines. Groups of assays that are related as part of a time series. Using regression correlation
2006-01-20 | E-GEOD-4072 | biostudies-arrayexpress
Project description: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
2006-03-07 | E-GEOD-4397 | biostudies-arrayexpress
Project description:Resistance to asparaginase, an antileukemic enzyme that depletes asparagine, is a common clinical problem. Using a genome-wide CRISPR/Cas9 screen, we found a synthetic lethal interaction between Wnt pathway activation and asparaginase in acute leukemias resistant to this enzyme. Wnt pathway activation induced asparaginase sensitivity in distinct treatment-resistant subtypes of acute leukemia, but not in normal hematopoietic progenitors. Sensitization to asparaginase was mediated by Wnt-dependent stabilization of proteins (Wnt/STOP), which inhibits GSK3-dependent protein ubiquitination and proteasomal degradation, a catabolic source of asparagine. Inhibiting the alpha isoform of GSK3 phenocopied this effect, and pharmacologic GSK3 inhibition profoundly sensitized drug-resistant leukemias to asparaginase. Our findings provide a molecular rationale for activation of Wnt/STOP signaling to improve the therapeutic index of asparaginase. To gain further insights into mechanisms of cytotoxicity of this combination, we applied unbiased mass spectrometry proteomics to CCRF-CEM cells, a human T-cell acute lymphoblastic leukemia cell line, treated with vehicle, asparaginase alone, the GSK3 inhibitor BRD0705 (which phenocopies Wnt/STOP pathway activation), or the combination of asparaginase and BRD0705.
2019-03-29 | PXD013061 | Pride
Project description: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.
2006-03-08 | GSE4397 | GEO
Project description:Clinical pediatric acute lymphoblastic leukemia samples after in vitro exposure to L-asparaginase
| PRJNA104897 | ENA
Project description:Time-series Gene Expression Profiling of Childhood Acute Lymphoblastic Leukemia
| PRJNA280632 | ENA
Project description:Taking the advantage of the human bone marrow (BM) scRNA-seq in Human cell atlas census of immune cells study, we resolved B lineage into comprehensive human B-cell development stages and identified their landscape in B-ALL. L-asparaginase is the cornerstone of combination protocols in acute lymphoblastic leukemia (ALL). After profiled B cell acute lymphoblastic leukemia (B-ALL) patient drug sensitivities ex vivo and applied network-based systems pharmacology analyses to examine signal circuitry, we revealed that the B-cell differentiation are correlated with the L-asparaginase response in B-ALL. Further multiomics analysis confirmed that L-asparaginase resistant B-ALL had higher percentage of Pre-pro-B like cells and less Pro-B like cells. By targeting BCL2, the key hub genes in Pre-pro-B cell network, Venetoclax combined with L-asparaginase can produce better outcome as demonstrated by in vitro and in vivo evaluations. In conclusion, our results identified B-ALL heterogeneity in L-asparaginase-resistant signature and BCL2 signaling and B-cell maturation stage, consistent with L-asparaginase response, providing unique opportunities for total clonal therapy.
2024-03-21 | GSE235787 | GEO