MicroRNA expression in CUTLL1 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE68612 | GEO | 2015/05/08
SECONDARY ACCESSION(S): PRJNA283205
REPOSITORIES: GEO
Similar Datasets
Project description:T-ALL cell line CUTLL1 was assessed for microRNA expression. Cells were treated with DMSO (ctr) or DAPT (10uM) to inhibit Notch1 cleavage for 3d and then harvested. 3 biological replicates were used per group (DMSO, n=3; DAPT, n=3).
2015-05-08 | E-GEOD-68612 | biostudies-arrayexpress
Project description:Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. CUTLL1 cell lines were treated with Compound E (GSI) or DMSO (solvent control). Cells were collected 12 h and 48 h after treatment. This was performed for 3 replicates. RNA-sequencing was performed on these samples.
2014-10-27 | E-GEOD-61999 | biostudies-arrayexpress
Project description:Notch is normally activated by cleavage and nuclear translocation of its intracellular domain (ICN1), which turns on downstream target genes. Human T cell acute lymphoblastic leukemia (T-ALL), an aggressive immature T cell malignancy, is associated with Notch 1 gain-of-function mutations in more than 50% of the cases. Efforts to date to identify direct Notch1 targets have been confounded by the lack of a method to turn Notch1 on in a controlled fashion in T-ALL cells that are poised to respond to Notch signals. Of note, because Notch signaling activates transcriptional repressors that feedback to dampen the expression of many target genes (a process referred to as incoherent logic), it is likely that many direct targets are missed in Notch off analyses, which are further complicated by an inability to identify direct targets in a clear-cut fashion. We have overcome this limitation by developing a GSI washout method that results in the rapid translocation of activated Notch1 to the nucleus. We intend to use this method to study the assembly and loading of transcriptional complexes onto downstream targets, the kinetics of target activation. To date, our efforts have been devoted to comparing the gene expression signature of Notch-on and Notch-off in the human T-ALL cell line CUTLL. In addition to previously identified Notch1 target genes, we have also identified a series of novel genes upregulated by GSI washout in the presence of cycloheximide, suggesting that they are likely to be direct targets. Additional controls included transduction of cells with dominant negative MAML1, a specific antagonist of canonical Notch1 signaling, prior to Notch1 reactivation, and a mock GSI washout to control for cycloheximide effects. CUTLL1 cells are cultured in triplicates with different treatments. Total RNA was prepared and hybridized to Affymetrix human U133 plus 2.0 microarrays
2011-07-06 | E-GEOD-29544 | biostudies-arrayexpress
Project description:Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. Gene expression was measured in the CUTLL1 T-ALL cell line after treatment with GSI or DMSO (solvent control). Cells were collected 12h and 48h after treatment. This was performed for 3 replicates.
2014-10-27 | E-GEOD-61869 | biostudies-arrayexpress
Project description:We identify perhexiline, a small molecule inhibitor of mitochondrial carnitine palmitoyltransferase-1, as a HES1-signature antagonist drug with robust antileukemic activity against NOTCH1 induced leukemias in vitro and in vivo. RNA-Seq from CUTLL1 cell lines treated with Perhexiline or vehicle for 3 days
2015-05-07 | E-GEOD-66014 | biostudies-arrayexpress
Project description:Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors (GSI), which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Analysis of gene expression in GSI-responsive and GSI-resistant cell lines treated with Compound E identifies differential resopnses to GSI. Keywords: Drug response Samples for microarray analysis were prepared and hybridized in Affymetrix Human U133 Plus 2.0 arrays according to the manufacturerâs instructions and as previously described. RNA was extracted from duplicate cultures of GSI-sensitive (ALL-SIL, CUTLL1, DND41, HPB-ALL, KOPTK1) and GSI-resistant (CCRF-CEM, MOLT3, P12 ICHIKAWA, PF382 and RPMI8402) T-ALL cell lines treated for 24 h with vehicle (DMSO) or 500 nM CompE. Interarray intensity differences were normalized with Dchip.
2008-08-20 | E-GEOD-5716 | biostudies-arrayexpress
Project description:Analysis of RNA-seq gene expression signatures in CUTLL3 ETP-ALL and CUTLL1 T-ALL cell lines
2021-10-21 | GSE164928 | GEO
Project description:Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia.
2014-10-27 | GSE61999 | GEO
Project description:Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors, which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Here we show that NOTCH1 regulates PTEN expression and the activity of the PI3K-AKT signaling pathway in normal and leukemic T cells. Notch signaling and the PI3K-AKT pathway synergize in vivo in a Drosophila model of Notch-induced tumorigenesis, and mutational loss of PTEN is associated with increased glycolysis and resistance to NOTCH1 inhibition in human T-ALL. These findings identify the transcriptional regulation of PTEN and the control of cellular metabolism as key elements of the oncogenic program activated by NOTCH1 and provide the basis for the design of new therapeutic strategies for T-ALL. Experiment Overall Design: Samples for microarray analysis were prepared and hybridized in Affymetrix Human U133 Plus 2.0 arrays according to the manufacturerâs instructions and as previously described. RNA was extracted from duplicate cultures of GSI-sensitive (ALL-SIL, CUTLL1, DND41, HPB-ALL, KOPTK1) and GSI-resistant (CCRF-CEM, MOLT3, P12 ICHIKAWA, PF382 and RPMI8402) T-ALL cell lines treated for 24 h with vehicle (DMSO) or 500 nM CompE. Interarray intensity differences were normalized with Dchip
2008-06-14 | E-GEOD-5682 | biostudies-arrayexpress
Project description:To formally address the biological activity of HES1 in vitro, we measured the transcriptional effect of HES1 inactivation infectiing CUTLL1 leukemia cell lines with shHES1 HES1 knockdown triggered apoptosis in human T-ALL lymphoblasts. We show that HES1 inactivation induces programmed cell death in leukemia lymphoblasts
2015-05-07 | GSE65872 | GEO