Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular profiling of LGL leukemia reveals role of sphingolipid signaling of cytotoxic lymphocytes

ABSTRACT: We used microarrays to expression profile peripheral blood mononuclear cells (PBMCs) from LGL leukemia patients and control subjects to identify survival pathways that render leukemic LGL resistant to activation induced cell death. Keywords: granular lymphocyte leukemia, PBMC

ORGANISM(S): Homo sapiens

PROVIDER: GSE10631 | GEO | 2008/05/01

SECONDARY ACCESSION(S): PRJNA107699

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of human peripheral blood mononuclear cells isolated from LGL leukemia samples reveals role of sphingolipid signaling of cytotoxic lymphocytes

Project description:We used microarrays to expression profile peripheral blood mononuclear cells (PBMCs) from LGL leukemia patients and control subjects to identify survival pathways that render leukemic LGL resistant to activation induced cell death. Experiment Overall Design: Leukemic PBMC RNA from 30 patients was extracted for target preparation and hybridization onto Affymetrix microarrays. We also isolated PBMCs and PBMCs subjected to enrichment for CD8+ cells from control patients. RNA from these cells (naÃ¯ve or activated with phytohemagglutinin) was extracted for target preparation and hybridization onto Affymetrix microarrays.

2008-06-11 | E-GEOD-10631 | biostudies-arrayexpress

Involvement of hCMV in the ontogeny of CD4+ T-LGL

2008-09-01 | GSE12488 | GEO

miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia [sRNA-Seq]

Project description:TCRαβ CD8 large granular lymphocyte (LGL) leukemia is a rare heterogeneous hematological disorder with a chronic disease course that mostly affects elderly. It is generally accepted that LGL cells arise as a consequence of chronic antigenic stimulation and inflammation and thrive because of dysregulation of mainly the STAT3 but also to some extent the ERK pathway, which are constitutively activated. In approximately 40% of patients this is due to STAT3 activating mutations, but for the other 60% it remains to be elucidated, why the STAT3 pathway is chronically activated. miRNAs are one of the most potent regulators in health and disease and are also linked with various leukemias. Therefore, we hypothesized that aberrant miRNA expression could contribute to dysregulation of the STAT3 pathway. miRNA sequencing in LGL leukemia cases and aged-matched healthy control TEMRA cells revealed overexpression of miRNA181a. Furthermore, gene set enrichment analysis (GSEA) of miRNA181a implicated its involvement in the STAT3 and ERK1/2 pathways. Phosphoflow analysis of STAT3, ERK1/2 in miR181a-transfected human CD8 T cells revealed that miR181a overexpression results in STAT3 and ERK1/2 phosphorylation. By using TL1, a human T-LGL cell line model, we have now established that miR181a is the common actor in T-LGL leukemia, driving STAT3 activation by SOCS3 inhibition in LGL leukemia patients. Additionally, miR181a induces ERK1/2 phosphorylation by inhibition of DUSP6. Taken together, our data show that miR181a is the missing link to explain why STAT3-unmutated patients show hyperactive STAT3.

2021-12-01 | GSE159878 | GEO

miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia [RNA-Seq]

2021-12-01 | GSE159819 | GEO

Transcription profiling of human CMV-stimulated CD69+, hCMV-stimulated CD69- and unstimulated monoclonal CD4+ T-LGL lymphocytes from peripheral blood samples from four TCRVbeta+/CD4+ T-LGL lymphocytosis patients

Project description:Recent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal TCRalphabeta+/CD4+/NKa+/CD8-/+dim T-large granular lymphocyte (LGL) lymphocytosis. Since healthy individuals show (oligo)clonal expansions of hCMV-specific TCRVbeta+/CD4+/cytotoxic/memory T-cells, we investigate the potential involvement of hCMV in the origin and/or expansion of monoclonal CD4+ T-LGL. A detailed characterization of those genes that underwent changes in T-LGL cells responding to hCMV was performed by microarray gene expression profile (GEP) analysis. Experiment Overall Design: Total RNA was isolated from magnetic-activated cell sorter (MACS)-freshly purified hCMV-stimulated CD69+, hCMV-stimulated CD69- and unstimulated monoclonal CD4+ T-LGL lymphocytes from PB samples from four TCRVbeta+/CD4+ T-LGL lymphocytosis patients (purity of â?¥98%). Briefly, 100 ng of total RNA from each of the 12 purified cell fractions was amplified and labeled using the GeneChip two cycle cDNA synthesis kit and the GeneChip IVT labeling kit (Affymetrix Inc., Santa Clara, CA), respectively. Then it was hybridized to the Human Genome U133 Plus 2.0 Array (Affymetrix). Experiment Overall Design: In parallel, total RNA was also isolated from highly purified (â?¥ 98% purity) hCMV-stimulated (specific) CD69+ CD4+ T-lymphocytes isolated from PB samples from hCMV-seropositive healthy donors (n=5, mean age of 36 years) using a FACSAria flow cytometer (BDB). To get pure and highly concentrated RNA, the silica membrane technology NucleoSpinÂ® RNA XS (Macherey-Nagel, DÃ¼ren, Germany) was used. Total RNA was then amplified, labeled and hybridized to the Human Genome U133 Plus 2.0 Array (Affymetrix) as described above.

2008-10-25 | E-GEOD-12488 | biostudies-arrayexpress

Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes.

Project description:T-cell large granular lymphocyte (LGL) leukemia is characterized by clonal expansion of CD3(+)CD8(+) cells. Leukemic LGLs correspond to terminally differentiated effector-memory cytotoxic T lymphocytes (CTLs) that escape Fas-mediated activation-induced cell death (AICD) in vivo. The gene expression signature of peripheral blood mononuclear cells from 30 LGL leukemia patients showed profound dysregulation of expression of apoptotic genes and suggested uncoupling of activation and apoptotic pathways as a mechanism for failure of AICD in leukemic LGLs. Pathway-based microarray analysis indicated that balance of proapoptotic and antiapoptotic sphingolipid-mediated signaling was deregulated in leukemic LGLs. We further investigated sphingolipid pathways and found that acid ceramidase was constitutively overexpressed in leukemic LGLs and that its inhibition induced apoptosis of leukemic LGLs. We also showed that S1P(5) is the predominant S1P receptor in leukemic LGLs, whereas S1P(1) is down-regulated. FTY720, a functional antagonist of S1P-mediated signaling, induced apoptosis in leukemic LGLs and also sensitized leukemic LGLs to Fas-mediated death. Collectively, these results show a role for sphingolipid-mediated signaling as a mechanism for long-term survival of CTLs. Therapeutic targeting of this pathway, such as use of FTY720, may have efficacy in LGL leukemia.

| S-EPMC2481553 | biostudies-literature

Genomic Architecture of LGL leukemia

Project description:Genomic Architecture of LGL leukemia

| PRJNA702838 | ENA

Genomic Architecture of LGL leukemia

Project description:Genomic Architecture of LGL leukemia

| PRJNA702839 | ENA

Expression data from patients with large granular lymphocyte leukemia

Project description:Our results suggest that STAT3 can be activated independent of key oncogenic driver mutations in its SH2 domain in a subset of patients with large granular lymphocyte disorders. We examined the gene expression pattern in T-LGL leukemias compared to controls, and the impact of the presence of STAT3 mutations on the transcriptional regulation of a specific set of genes previously described.

2012-08-03 | GSE39838 | GEO

Lgl protein interactome - Lgl reduces endosomal vesicle acidification and Notch signaling by promoting the interaction between Vap33 and the V-ATPase complex

Project description:To identify Lgl binding proteins, we purified Lgl-containing protein complexes from cultured Drosophila S2 cells, using the single-step streptavidin purification from stable cell lines expressing SBP-tagged Lgl, followed by nanoLC-MS/MS analysis of the interactors. This study revealed the binding of Lgl to Vap33, which we further connected to the function of the vacuolar ATPase and regulation of Notch signaling.

2018-06-10 | PXD009568 | Pride

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