Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq of NOTCH1 mutation in chronic lymphocytic leukemia cell BaF3.

ABSTRACT: The hotspot c.7541_7542delCT NOTCH1 mutation has been proven to have a unfavorable clinical impact in chronic lymphocytic leukemia (CLL). The aim of our study was to investigate the influence of NOTCH1 mutation(c.7541_7542delCT) on NOTCH1 signaling in CLL cells using Gene Expression Profiling.

ORGANISM(S): Mus musculus

PROVIDER: GSE115728 | GEO | 2021/03/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of NOTCH1 bound genes in chronic lymphocytic leukaemia (CLL) cells

Project description:NOTCH1 is mutationally activated in ~15% of cases of chronic lymphocytic leukaemia (CLL), but its role in B-cell development and leukemogenesis is not known. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ~50% of peripheral blood CLL cases lacking gene mutations. We identify a ‘NOTCH1 CLL gene expression signature’ in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival and signal transduction physiology. In particular, we show that MYC is a direct target of NOTCH1 via B-cell specific distal regulatory elements, thus implicating this oncogene in the pathogenesis of the disease.

2017-03-24 | GSE92701 | GEO

Identification of genes induced by NOTCH1 in a chronic lymphocytic leukaemia (CLL) cell line and tracking of these genes in primary CLL patients

2017-03-24 | GSE92626 | GEO

Retroviral transduction of NOTCH1 into primary human Chronic Lymphocytic Leukemia cells unravels immune escape-mechanisms

Project description:Functional studies to investigate gene mutations recurrent in B cell lymphoma have been hampered by the inability to genetically manipulate primary cells, attributed to low transduction efficacy and procedure-associated toxicity. Alternative approaches utilize cell lines and mouse models, which often only poorly represent the genomic complexity and biology of the primary malignancy. To overcome these limitations, we have developed a method to retrovirally transfer genes into primary malignant B cells with high transduction efficacy and minimal toxicity. Using this method, we investigated the functions of NOTCH1, the most commonly mutated gene in CLL, by generating isogenic primary tumor cells from patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), differing only in their expression of NOTCH1. Our data demonstrate that NOTCH1 facilitates immune escape of malignant B cells by up-regulating PD-L1, partly dependent on autocrine interferon-g signaling. In addition, NOTCH1 causes silencing of the entire HLA-class II locus via suppression of the transcriptional co-activator CIITA. These NOTCH1-mediated immune escape mechanisms are associated with the expansion of CD4+ T cells in vivo, further contributing to the poor clinical outcome of NOTCH1-mutated CLL and MCL

2022-08-26 | PXD024112 | Pride

RNA-seq of NOTCH1 mutation in chronic lymphocytic leukemia cell BaF3.

Project description:RNA-seq of NOTCH1 mutation in chronic lymphocytic leukemia cell BaF3.

| PRJNA475876 | ENA

Gene expression study in WT and NOTCH1 mutated CLL cells.

Project description:Stabilizing mutations of NOTCH1 have been identified in about 10% of chronic lymphocytic leukemia (CLL) cases at diagnosis, with a higher frequency in unmutated IGHV (IGHV-UM) CLL, chemorefractory CLL and CLL in advanced disease phases. Clinically, the presence of NOTCH1 mutations is an independent predictor of overall survival in CLL and associates with resistance to anti-Cd20 immunotherapy. The Gene Expression Profile was generated to identify the peculiar molecular signatures of NOTCH1 mutated CLL in the context of IGHV-UM CLL. Constitutive gene expression in CLL cells bearing or not NOTCH1 mutation (c.7541_7542delCT). Five samples were selected for each category (WT vs MUT).

2016-03-01 | E-GEOD-75122 | biostudies-arrayexpress

Gene expression study in WT and NOTCH1 mutated CLL cells.

2016-03-01 | GSE75122 | GEO

Active AKT Signaling triggers CLL towards Richter's transformation via over-activation of Notch1

Project description:Richter's syndrome (RS) is an aggressive transformation of Chronic Lymphocytic Leukaemia (CLL) frequently due to TP53, CDKN2, MYC or NOTCH1 mutations. whereas a significant proportion displays no specifically acquired driver mutation. We observe constitutive AKT phosphorylation not only in high-risk CLL patients harbouring p53 and NOTCH mutations but also in numerous RS patients. Consistently, genetic over-activation of AKT within the Eµ-TCL1 CLL mouse model results in a high-grade lymphoma phenotype of Richters syndrome. Multiomics assessment of our novel mouse model revealed a S100 defined subcluster of highly proliferative lymphoma cells developing from indolent CLL-like B-cells as a consequence of sudden NOTCH activation being fueled by enhanced NOTCH ligand exposure from T-cells in the microenvironment. Our data link AKT and NOTCH signaling in patient samples, genomic alterations, phosphoproteome and single-cell transcriptome profiles. Collectively, we have identified active AKT as a causative transforming pathway of indolent CLL towards aggressive RS thus providing novel mechanistic insights into the molecular understanding of RS.

2021-02-25 | PXD017457 | Pride

Histone H3 lysine 27 acetylation (H3K27ac) profile of primary CLL cells transduced with a retrovirus expressing mutated NOTCH1

Project description:In chronic lymphocytic leukemia (CLL), NOTCH1 is the most commonly mutated gene at diagnosis and it is associated with a poor outcome. The mechanisms underlying how NOTCH1 contributes to disease progression, resistance to treatment and Richter’s transformation remain largely unknown. The main goal of this study is to compare the chromatin activation profile of primary CLL cells transduced with the intracellular part of NOTCH1 lacking of the PEST domain vs. cells transduced with an empty vector. Additionally, patients with the Trisomy 12 abnormality are included in this study to clarify the role of the mutations in this specific sub-group of CLL patients that are strongly associated with NOTCH1 mutations.

2022-09-08 | GSE166727 | GEO

The effects of U1 snRNA mutation in chronic lymphocytic leukemia cell lines

Project description:Despite an intensive search for non-coding cancer drivers, only a few have been discovered to date and none have been found among the RNAs contributing to the spliceosome. Here we report a highly recurrent A>C somatic mutation at the third base of U1 spliceosomal RNA in several tumour types. This mutation changes the preferential A-U base-pairing between U1 and 5′ splice site to C-G base-pairing, thereby creating novel splice junctions and altering the splice pattern of multiple genes, including those related to cancer. Clinically, the A>C mutation is associated with alcohol consumption in hepatocellular carcinoma and the aggressive IGHV unmutated subtype of chronic lymphocytic leukaemia (CLL). The U1 hotspot mutation confers an adverse prognosis to CLL patients independently, and may represent a new target for treatment. Our study demonstrates one of the first non-coding drivers in spliceosomal RNAs and reveals a novel mechanism of aberrant splicing in human cancer.

2019-07-13 | GSE134197 | GEO

Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA

Project description:Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA: prognostic factors and interaction with the microenvironment. Zeta-associated protein 70 (ZAP70) is a widely recognized prognostic factor in chronic lymphocytic leukemia (CLL), but mechanisms by which its higher expression leads to a poor outcome remain to be fully explained. In an attempt to unveil unfavorable cellular properties linked to high ZAP70 expression, we used gene expression profiling to identify genes associated with disparities in B-cells from CLL patients expressing high versus low ZAP70 mRNA, measured by quantitative real-time PCR. Keywords: comparison of poor and good prognosis CLL patient transcriptome regarding ZAP70 expression

2009-04-18 | GSE12734 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data