Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiR-543 regulates the epigenetic landscape of myelofibrosis by targeting TET1 and TET2 [miRNA]

ABSTRACT: We analyzed 14 patients with Myelofibrosis (MF) to determine the miRNA profile of patients not responding to current MF treatment. We used Affymetrix miRNA-3 array to profile the differentially expressed miRNA in bone-marrow between patients with MF that respond to current MF treatment and the patients with MF that do not respond to current MF treatment.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE142239 | GEO | 2019/12/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Clinical drug response and proteotype profiling elucidates targetable vulnerabilities of myelofibrosis

Project description:Myelofibrosis (MF) is a hematopoietic stem cell disorder belonging to the myeloproliferative neoplasms. MF patients frequently carry driver mutations in JAK2 and Calreticulin (CALR) and have limited therapeutic options. Here, we integrate ex vivo drug response and proteotype analyses across MF patient cohorts to discover targetable vulnerabilities and associated therapeutic strategies. Drug sensitivities of mutated and progenitor cells were measured in patient blood using high-content imaging and single-cell deep learning-based analyses. Integration with matched molecular profiling revealed three therapeutic vulnerabilities. First, CALR mutations drive BET and HDAC inhibitor sensitivity, particularly in the absence of high MAPK-Ras pathway protein levels. Second, an MCM complex-high proliferative signature corresponds to advanced disease and sensitivity to drugs targeting pro-survival signaling and DNA replication. Third, homozygous CALR mutations result in high ER stress, responding to ER stressors and UPR inhibition. Overall, our integrated analyses provide a molecularly-motivated roadmap for individualized MF patient treatment.

2023-10-12 | PXD036075 | Pride

Gene expression profiling of granulocytes from primary and secondary myelofibrosis

Project description:Primary myelofibrosis (PMF) together with polycythemia vera (PV) and essential thrombocythemia (ET) belongs to the classic Philadelphia-negative myeloproliferative neoplasms (MPNs). PV and ET can evolve to secondary myelofibrosis (SMF) giving rise to post-PV (PPV) and post-ET (PET) myelofibrosis (MF). PMF and SMF patients are currently managed in the same way and prediction of survival is based on the same prognostic models, even if it has been demonstrated that they can’t accurately distinguish different risk categories in SMF. In the last few years interest grew concerning the ability of gene expression profiling (GEP) to provide valuable prognostic information for clinical decision making. To construct a molecular signature that can predict survival according to gene expression we studied GEP of granulocytes from 114 MF patients, including 35 prefibrotic/early PMF (Pre-PMF), 37 overt PMF (Overt-PMF), 26 PET and 16 PPV, using microarray platform.

2021-03-09 | GSE159514 | GEO

Inflammatory gene expression associated with advanced myelofibrosis

Project description:Myelofibrosis (MF) is a progressive, bone marrow (BM) malignancy associated with monocytosis, and is believed to promote the pathological remodelling of the extracellular matrix. Here, we show that the pathologic grading of MF was associated with inflammatory gene expression in primary patient samples.

2022-07-11 | GSE206768 | GEO

Longitudinal inflammatory gene expression associated with advanced myelofibrosis

2022-07-11 | GSE206770 | GEO

Inhibition of CDK6 using Palbociclib in combination with Ruxolitinib markedly improves myelofibrosis in murine models

Project description:Myelofibrosis (MF) is a deadly blood neoplasia that presents the worst prognosis among myeloproliferative neoplasms (MPN). Expression of CDK6 is significantly elevated in MPN/MF hematopoietic progenitor cells. In this study, we investigated the efficacy of CDK4/6 inhibitor Palbociclib alone or in combination with Ruxolitinib in Jak2V617F and MPLW515L murine models of MF. Treatment of Palbociclib alone significantly reduced leukocytosis, splenomegaly and inhibited bone marrow fibrosis in Jak2V617F and MPLW515L mouse models of MF. Combined treatment of Palbociclib and Ruxolitinib resulted in normalization of peripheral blood leukocyte counts, marked reduction of spleen size and abrogation of bone marrow fibrosis in murine models of MF. Mechanistically, we show that Palbociclib treatment or depletion of CDK6 inhibits Aurora kinase, NF-κB and TGF-β signaling pathways in Jak2V617F mutant hematopoietic cells. Overall, our data suggest that Palbociclib in combination with Ruxolitinib may have therapeutic potential for treatment of MF.

2021-11-05 | GSE173814 | GEO

miR-543 regulates the epigenetic landscape of myelofibrosis by targeting TET1 and TET2.

Project description:Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by cytopenia and extramedullary hematopoiesis, resulting in splenomegaly. Multiple pathological mechanisms (e.g., circulating cytokines and genetic alterations, such as JAKV617F mutation) have been implicated in the etiology of MF, but the molecular mechanism causing resistance to JAK2V617F inhibitor therapy remains unknown. Among MF patients who were treated with the JAK inhibitor ruxolitinib, we compared noncoding RNA profiles of ruxolitinib therapy responders versus nonresponders and found miR-543 was significantly upregulated in nonresponders. We validated these findings by reverse transcription-quantitative PCR. in this same cohort, in 2 additional independent MF patient cohorts from the United States and Romania, and in a JAK2V617F mouse model of MF. Both in vitro and in vivo models were used to determine the underlying molecular mechanism of miR-543 in MF. Here, we demonstrate that miR-543 targets the dioxygenases ten-eleven translocation 1 (TET1) and 2 (TET2) in patients and in vitro, causing increased levels of global 5-methylcytosine, while decreasing the acetylation of histone 3, STAT3, and tumor protein p53. Mechanistically, we found that activation of STAT3 by JAKs epigenetically controls miR-543 expression via binding the promoter region of miR-543. Furthermore, miR-543 upregulation promotes the expression of genes related to drug metabolism, including CYP3A4, which is involved in ruxolitinib metabolism. Our findings suggest miR-543 as a potentially novel biomarker for the prognosis of MF patients with a high risk of treatment resistance and as a potentially new target for the development of new treatment options.

| S-EPMC7030823 | biostudies-literature

miR-543 regulates the epigenetic landscape of myelofibrosis by targeting TET1 and TET2.

Project description: Not available

| S-EPMC10967479 | biostudies-literature

MiR-543 regulates the epigenetic landscape of myelofibrosis by targeting TET1 and TET2 [miRNA]

Project description:MiR-543 regulates the epigenetic landscape of myelofibrosis by targeting TET1 and TET2 [miRNA]

| PRJNA596272 | ENA

Genome-wide analysis of enhancer-related DNA methylation in myelofibrosis reveals ZFP36L1 as a potential tumor suppressor gene

Project description:In this study we have interrogated the DNA methylome of myelofibrosis (MF) patients using high-density DNA methylation arrays. Interestingly, primary and secondary MF showed no differences in DNA methylation profiles, whereas a total of 35,238 differentially methylated CpGs (DMC) corresponding to 10,904 genes were detected between MF patients and healthy controls. Remarkably, the majority of DMCs were located outside gene promoter regions and significantly associated with enhancer regions. This enhancer aberrant hypermethylation showed a negative correlation with the expression of 27 genes in the MF patient cohort. Of these, we focused on ZFP36L1 gene and validated its decreased expression and enhancer DNA hypermethylation in an independent cohort of MF patients and myeloid cell-lines. In vitro reporter assay and 5’ azacitidine treatment confirmed the functional relevance of the intronic-enhancer hypermethylation of ZFP36L1. Finally, in vitro rescue of ZFP36L1 expression had an impact in cell proliferation and induced apoptosis in SET-2 cell line indicating a possible role of ZFP36L1 as a tumor suppressor gene in MF. Overall, we describe for the first time the MF DNA methylation profile, showing enhancer DNA hypermethylation as a potential functional mechanism playing an important role in silencing of a tumor suppressor gene in this disease.

2019-08-27 | GSE118241 | GEO

Gene expression of human littoral cells and splenic vascular endothelial cells from the spleens of normal individuals and patients with myelofibrosis

Project description:The vascular lining cells in the human spleens include littoral cells (LCs) and other splenic vascular endothelial cells (SVECs). LCs that comprise about 30 percent of the splenic red pulp are specialzed endothelial cells distinct from SVECs. They line the splenic sinusoids and function as the filters and scavengers for senescent or altered red blood cells. Patients with advanced forms of myelofibrosis (MF) often develope extramedullary hematopoiesis in the spleen.Vascular lining cells within MF spleens are thought to serve as a supportive microenvironment for MF hematopoietic cells. In this study we isolated MF and normal LCs and SVECs from human spleens using immunostaining and flow cytometric sorting and used microarrays to analyze the underling mechanism of LCs' unique functions that distinguish them from SVECs, and the properties of MF LCs and SVECs and their contributions to the microenvironment of MF spleens.

2018-05-30 | GSE106532 | 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