Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Fatima Al-Shahrour

PROVIDER: E-GEOD-54646 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis.

Rampal Raajit R Al-Shahrour Fatima F Abdel-Wahab Omar O Patel Jay P JP Brunel Jean-Philippe JP Mermel Craig H CH Bass Adam J AJ Pretz Jennifer J Ahn Jihae J Hricik Todd T Kilpivaara Outi O Wadleigh Martha M Busque Lambert L Gilliland D Gary DG Golub Todd R TR Ebert Benjamin L BL Levine Ross L RL

Blood 20140416 22

Genomic studies have identified somatic alterations in the majority of myeloproliferative neoplasms (MPN) patients, including JAK2 mutations in the majority of MPN patients and CALR mutations in JAK2-negative MPN patients. However, the role of JAK-STAT pathway activation in different MPNs, and in patients without JAK2 mutations, has not been definitively delineated. We used expression profiling, single nucleotide polymorphism arrays, and mutational profiling to investigate a well-characterized c ...[more]

PMID: 24740812

Similar Datasets

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [HEL cell lines]

Project description:We used expression profiling, SNP arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. Conversely, we identified a gene expression signature of CALR mutations; this signature was significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK mutational status are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis. [HEL cell lines] We have performed gene expression profiling in the JAK2V617F homozygous mutant HEL cell line following treatment with 2 independent shRNAs targeting JAK2 or 2 different control shRNAs

2014-06-03 | E-GEOD-54645 | biostudies-arrayexpress

Griffiths JAK ESC

Project description:Transcriptional profiling comparison of mouse embryonic stem cells versus their JAK mutated counterparts, cultured both in the presence and absence of LIF (leukemia inhibitory factor).

2011-04-18 | E-MTAB-416 | biostudies-arrayexpress

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis.

Project description:Genomic studies have identified somatic alterations in the majority of myeloproliferative neoplasms (MPN) patients, including JAK2 mutations in the majority of MPN patients and CALR mutations in JAK2-negative MPN patients. However, the role of JAK-STAT pathway activation in different MPNs, and in patients without JAK2 mutations, has not been definitively delineated. We used expression profiling, single nucleotide polymorphism arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. Conversely, we identified a gene expression signature of CALR mutations; this signature was significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK2 mutational status, are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis.

| S-EPMC4041169 | biostudies-literature

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-06-03 | GSE54646 | GEO

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [MPN patients]

Project description:We used expression profiling, SNP arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. Conversely, we identified a gene expression signature of CALR mutations; this signature was significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK mutational status are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis. [MPN patients] We have performed microarray gene expression analysis in 93 patients with MPNs (28 PV, 47 ET, 18 MF) and 11 age-matched normal donors.

2014-06-03 | E-GEOD-54644 | biostudies-arrayexpress

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [MPN patients]

2014-06-03 | GSE54644 | GEO

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [HEL cell lines]

2014-06-03 | GSE54645 | GEO

Cooperative Epigenetic Modulation by Cancer Amplicon Genes

Project description:Amplification of a ~2.5 megabase region on chromosome 9p24 is frequent in both primary mediastinal B-cell lymphoma (PMBL) and Hodgkin's lymphoma (HL). To identify the oncogenic genes in this interval, we created a RNA interference library targeting amplicon genes. A genetic screen using this library identified three genes that are essential for the proliferation and survival of PMBL and HL lines with this amplicon, which encode the kinase JAK2, the histone demethylase JMJD2C and a gene of unknown function, RANBP6. Inhibition of JAK2 and JMJD2C cooperated in killing these lymphomas and in remodeling their chromatin by globally increasing trimethylation of lysine 9 on histone H3 (H3K9me3) and heterochromatin formation. JAK2 and JMJD2C inhibition silenced MYC and its target genes, which coincided with an increase in H3K9me3 and the heterochromatin protein HP1alpha at the MYC locus. We conclude that amplification of JAK2 and JMJD2C cooperatively reprograms the PMBL and HL epigenome, sustaining their survival and proliferation. Signal from untreated shRNA cells or DMSO control cells (Cy3) was compared to 4 dox-treated JAK2 shRNA cells, 4 dox-treated JMJD2C shRNA cells, or 8 JAK2 inhibitor-treated cells (Cy5).

2011-01-04 | E-GEOD-20988 | biostudies-arrayexpress

Evolution of the JAK-STAT pathway.

Project description:The JAK-STAT pathway represents a finely tuned orchestra capable of rapidly facilitating an exquisite symphony of responses from a complex array of extracellular signals. This review explores the evolution of the JAK-STAT pathway: the origins of the individual domains from which it is constructed, the formation of individual components from these basic building blocks, the assembly of the components into a functional pathway, and the subsequent reiteration of this basic template to fulfill a variety of roles downstream of cytokine receptors.

| S-EPMC3670263 | biostudies-literature

C9ORF72 suppresses JAK-STAT mediated inflammation.

Project description:Hexanucleotide repeat expansion in the gene C9ORF72 is a leading cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). C9ORF72 deficiency leads to severe inflammatory phenotypes in mice, but exactly how C9ORF72 regulates inflammation remains to be fully elucidated. Here, we report that loss of C9ORF72 leads to the hyperactivation of the JAK-STAT pathway and an increase in the protein levels of STING, a transmembrane adaptor protein involved in immune signaling in response to cytosolic DNA. Treatment with a JAK inhibitor rescues the enhanced inflammatory phenotypes caused by C9ORF72 deficiency in cell culture and mice. Furthermore, we showed that the ablation of C9ORF72 results in compromised lysosome integrity, which could contribute to the activation of the JAK/STAT-dependent inflammatory responses. In summary, our study identifies a mechanism by which C9ORF72 regulates inflammation, which might facilitate therapeutic development for ALS/FTLD with C9ORF72 mutations.

| S-EPMC10214391 | biostudies-literature

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