Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells [methylation]

ABSTRACT: Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells [methylation]

PROVIDER: PRJNA857305 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells [methylation]

Project description:IDH mutations are found in 20% of acute myeloid leukemia (AML) patients. IDH inhibitors (IDHi) have emerged as a novel treatment option. However, only 30-40% of patients respond to single drug treatment and there is an unmet need for improvement as well as identifying alternative treatment options. The overall aim of this study was therefore to gain deeper insights into the molecular signatures of IDH mutations, the effects of IDHi as well as to identify a molecular vulnerability to tailor novel therapies for AML patients with IDH mutations. Here, we have characterized the transcriptional and epigenetic landscape before and after treatment with IDH2i AG-221, using an IDH2 mutated AML cell line model and AML patient cohorts. We discovered decreased DNA hydroxymethylation in IDH2 mutated AML cells, particular in enhancers and a perturbed transcriptional regulatory network involving myeloid transcription factors. In addition, hypermethylation of the HLA I cluster caused a dramatic down-regulation of HLA genes, triggering an enhanced natural killer (NK) cell activation, and displayed an increased susceptibility to NK cell mediated killing. These responses were reverted when the AML cells were pre-exposed to IFN-gamma, resulting in up-regulation of cell surface HLA class I. Finally, analyses of DNA methylation data from IDHi-treated patients showed that non-responders continued to harbor hypermethylation in HLA class I genes, suggesting maintained susceptibility to NK cells. In conclusion, this study provides new insights into the perturbed epigenetic and transcriptional regulation in IDH mutated AML and shed light on a potential strategy for personalized medicine in AML. Methylation/hydroxymethylation profiling by array

2023-07-09 | GSE207829 | GEO

Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells [TT-Seq]

2023-07-09 | GSE207830 | GEO

Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells

Project description:Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells

| PRJNA857302 | ENA

Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells [TT-Seq]

Project description:Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells [TT-Seq]

| PRJNA857306 | ENA

Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells.

Project description:Isocitrate dehydrogenase (IDH) mutations are found in 20% of acute myeloid leukemia (AML) patients. However, only 30-40% of the patients respond to IDH inhibitors (IDHi). We aimed to identify a molecular vulnerability to tailor novel therapies for AML patients with IDH mutations. We characterized the transcriptional and epigenetic landscape with the IDH2i AG-221, using an IDH2 mutated AML cell line model and AML patient cohorts, and discovered a perturbed transcriptional regulatory network involving myeloid transcription factors that were partly restored after AG-221 treatment. In addition, hypermethylation of the HLA cluster caused a down-regulation of HLA class I genes, triggering an enhanced natural killer (NK) cell activation and an increased susceptibility to NK cell-mediated responses. Finally, analyses of DNA methylation data from IDHi-treated patients showed that non-responders still harbored hypermethylation in HLA class I genes. In conclusion, this study provides new insights suggesting that IDH mutated AML is particularly sensitive to NK cell-based personalized immunotherapy.

| S-EPMC10457197 | biostudies-literature

Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells

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

2023-07-09 | GSE207831 | GEO

Genotyping by array of 297 adult-type diffuse gliomas comprise IDH-mutant astrocytomas, IDH-mutant 1p/19q codeleted oligodendrogliomas, and IDH-wildtype glioblastomas

Project description:Adult-type diffuse gliomas comprise IDH-mutant astrocytomas, IDH-mutant 1p/19q codeleted oligodendrogliomas (ODG), and IDH-wildtype glioblastomas (GBM). GBM display genome instability, which may result from two genetic events leading to massive chromosome alterations: chromothripsis (CT) and whole-genome duplication (WGD). The better prognosis of the latter may be related to their genome stability compared to GBM. Pangenomic profiles of 297 adult diffuse gliomas were analyzed at initial diagnosis using SNP arrays, including 192 GBM and 105 IDH-mutant gliomas (61 astrocytomas and 44 ODG). Tumor ploidy was assessed with Genome Alteration Print and CT events with CTLPScanner and through manual screening.

2024-12-24 | E-MTAB-13542 | biostudies-arrayexpress

Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis

Project description:This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO212 for the treatment of patients with radiographically-confirmed progression of Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype, and the safety, pharmacokinetics and efficacy of a repeated dose regimen of NEO212 when given with select SOC for the treatment of solid tumor patients with radiographically confirmed uncontrolled brain metastasis. The study will have three phases, Phase 1, Phase 2a and Phase 2b.

| 92735 | ecrin-mdr-crc

Expression from hemocytes misexpressing Idh-R195H vs. controls

Project description:Expression profile for hemocytes from hml-Gal4, UAS-2xEGFP larvae were compared to hemocytes from hml-Gal4, UAS-2xEGFP; UAS-Idh-R195H larvae We sought to determine which genes and pathways were upregulated or downregulated in hemocytes expressing Idh-R195H, the Drosophila homolog of the human cancer-associated IDH1-R132H mutant, in vivo. We sought to obtain homogeneous populations of hemocytes from each genotype. We compared larvae expressing Idh-R195H from the hml-Gal4 driver to larvae with the hml-Gal4 driver alone.

2014-10-03 | E-GEOD-62008 | biostudies-arrayexpress

RNA-seq of NK cells from blood samples of HV and AML patients

Project description:CD56neg CD16+ Natural Killer (NK) cells have been reported to expand in chronic diseases and acute myeloid leukemia (AML). However, their biological role is still unclear. Using bulk RNA-sequencing, we compared gene expression profile of CD56neg CD16+ NK cells with conventional CD56bright, CD56dim CD16- and CD56dim CD16+ NK cells from blood samples of HV and AML patients. RNA-seq unveiled that CD56neg CD16+ NK cells were mature circulating NK cells with functional capacities. Taken together, our results suggest that CD56neg CD16+ NK cells are a relevant target for future NK-cell-based immunotherapies.

2024-12-20 | E-MTAB-14569 | biostudies-arrayexpress

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