Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptomical characterization of T-Large Granular Lymphocyte Leukemia (T-LGLL) patients having different STAT3/STAT5B genetic status and clinical manifastations

ABSTRACT: T-Large Granular Lymphocyte Leukemia is a rare lymphoproliferative disorder characterized by the abnormal clonal expansion of cytotoxic T-LGL. The immunophenotype, clinical presentation, and prognosis are associated with activating mutations in STAT3 and STAT5B genes, which define four distinct subsets of the disease: CD8+ with STAT3 mutation, CD8+ wild-type, CD4+ with STAT5B mutation, and CD4+ wild-type. RNA-seq data analysis of these patients reveals aberrant genes and non-coding RNA expression, pathways dysregulation, and the peculiarities of STAT3 mutated cases, which are associated with severe symptoms. This study offers new insights into the pathogenesis and clinical characteristics of T-LGLL patients, highlighting potential new targetable oncogenic axes for this disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228868 | GEO | 2025/09/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Andersson_et_al_2013

Project description:LGL leukemia is chronic clonal lymphoproliferative disorder, characterized by expansion of cytotoxic CD8+ T-cells or NK-cells. We compared gene expression of 2 LGL leukemia patients with STAT3 mutation (Patients 11 and 12) and 2 LGL leukemia patients without STAT3/STAT5b mutation (Patients 9 and 10) with CD8 and CD4 samples from healthy controls to assess different gene expression patterns between samples.

2013-11-14 | E-MTAB-2068 | biostudies-arrayexpress

Rajala_et_al_2013

Project description:Large lymphocytic leukemia (LGL) is a chronic clonal lymphoproliferative disorder, characterized by expansion of cytotoxic CD8+ T-cells or NK-cells. We compared gene expression of 3 LGL leukemia patients with STAT3 mutation (Patients 1, 2, and 3), 3 LGL leukemia patients with STAT5b mutation (Patients 4, 5, and 6), and 2 LGL leukemia patients without STAT3/STAT5b mutation (Patients 7 and 8) with CD8 and NK-cell samples from healthy controls to assess different gene expression patterns between samples.

2013-04-15 | E-MTAB-1611 | biostudies-arrayexpress

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. Mononuclear cells were separated from peripheral blood by density gradient sedimentation (Mediatech, Herndon, VA, USA). LGL cells were separated by flow cytometric sorting using anti-VB and CD8 mAb as described previously. Healthy, donor-derived CD8+CD57+ cells were isolated by flow cytometric sorting using CD3, CD8, and CD57 mAb. Total RNA was extracted from cells using Trizol (Invitrogen, Carlsbad, CA, USA) Phase-Lock gel tubes (Eppendorf, Hamburg, Germany), cleaned RNAeasy columns (Qiagen, Valencia CA, USA), and dissolved diethylpyrocarbonate water. Total cRNA was prepared using the in vitro-transcribed (Affymetrix, Santa Clara, CA, USA) and hybridized to U133 arrays, according to the manufacturer's instructions (Affymetrix). All microarrays were examined for surface defects, grid placement, background intensity, housekeeping gene expression, and a 3:5 ratio of probe from genes of varying length. Expression analysis was conducted using standard Affymetrix analysis software algorithms (Microarray Suite 5.0). Comparative analysis between expression profiles was carried out on GeneSpring' software, Version 7.1 (Agilent, Clara, CA, USA). Scanned images of Affymetrix chips were converted spreadsheet numbers using Affymetrix proprietary GeneChip Operating software (GCOS).

2012-08-02 | E-GEOD-39838 | biostudies-arrayexpress

Two mutations associated with leukemia that change a single tyrosine residue in the STAT5B SH2 domain have opposite effects on the transcriptional programs controlling hematopoiesis [scRNA-seq]

Project description:Normal hematopoiesis is regulated by various cytokines via the JAK-STAT signaling pathway. Gene deletion studies in mice have demonstrated the crucial role of STAT5B in the proliferation, differentiation, and survival of immune cells. However, the physiological effects of human STAT5B mutations remain poorly understood. Mutations within the SH2 domain of STAT5B have been identified in leukemia patients. In this study, we investigate two specific variants: one that substitutes tyrosine 665 with phenylalanine (STAT5BY665F) and another that substitutes tyrosine 665 with histidine (STAT5BY665H). We introduced these two mutations into the mouse genome and observed distinct and divergent impacts on immune cell function. The STAT5BY665F mutation enhanced STAT5B activity and the establishment of transcriptional enhancers and genetic programs. Conversely, the STAT5BY665H mutation was largely inactive, failing to induce the interleukin-regulated enhancer landscape and gene expression. Both mutations modified immune cell profiles, inducing features characteristic of autoimmune disease. In STAT5BY665F mice, there was an expansion of CD8+ and regulatory CD4+ T cells, whereas STAT5BY665H mice didn’t. Both mutant strains exhibited skin abnormalities; however, only the STAT5BY665F mice developed progressive dermatitis. Introduction of equivalent mutations into STAT5A did not significantly impact hematopoiesis. However, mice carrying mutations in both STAT5A and STAT5B displayed additive effects with highly elevated CD4+ and CD8+ T cells. Our findings demonstrate that different naturally occurring missense mutations identified in leukemia patients, changing a single amino acid within the SH2 domain, can either activate or inactivate STAT5B and thereby impact T cell populations.

2025-02-12 | GSE276312 | GEO

Two mutations associated with leukemia that change a single tyrosine residue in the STAT5B SH2 domain have opposite effects on the transcriptional programs controlling hematopoiesis [RNA-seq]

2025-02-12 | GSE276311 | GEO

Two mutations associated with leukemia that change a single tyrosine residue in the STAT5B SH2 domain have opposite effects on the transcriptional programs controlling hematopoiesis [ChIP-seq]

2025-02-12 | GSE276308 | GEO

Expression data from patients with large granular lymphocyte leukemia

2012-08-03 | GSE39838 | GEO

miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia [RNA-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 | GSE159819 | GEO

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

2021-12-01 | GSE159878 | GEO

Microarray mRNA expression profiling in Stat5b knockdown pancreatic beta cell line

Project description:Stat5b gene is located at IDD4 type 1 diabetes susceptibility interval, and is mutated in NOD mice. This mutation has been linked to diabetes with strong association with autoimmune aetiology. We have treated MIN6 pancreatic beta cell line with Stat5b siRNA and analyzed the differential expression profile in control siRNA treated versus Stat5b siRNA treated cells in an effort to understand the role of Stat5b in diabetes.

2022-12-31 | GSE85496 | 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