Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA89525 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:TARGET: Acute Myeloid Leukemia (AML), Induction Failure Subproject
| PRJNA172041 | ENA
Project description:Gene expression profiling in Acute Myeloid Leukemia (AML)
| PRJNA157501 | ENA
Project description:Gene expression profiling of Acute Myeloid Leukemia (AML) samples
| PRJNA150437 | ENA
Project description:The bromodomain and extraterminal (BET) protein BRD4 is a therapeutic target in acute myeloid leukemia (AML). Here, we demonstrate that the AML maintenance function of BRD4 requires its interaction with NSD3, which belongs to a subfamily of H3K36 methyltransferases. Unexpectedly, AML cells were found to only require a short isoform of NSD3 that lacks the methyltransferase domain. We show that NSD3-short is an adaptor protein that sustains leukemia by linking BRD4 to the CHD8 chromatin remodeler, by using a PWWP chromatin reader module, and by employing an acidic transactivation domain. Genetic targeting of NSD3 or CHD8 mimics the phenotypic and transcriptional effects of BRD4 inhibition. Furthermore, BRD4, NSD3, and CHD8 colocalize across the AML genome, and each is released from super-enhancer regions upon chemical inhibition of BET bromodomains. These findings suggest that BET inhibitors exert therapeutic effects in leukemia by evicting BRD4-NSD3-CHD8 complexes from chromatin to suppress transcription. ChIP-Seq for regulatory factors of BRD4, NSD3, CHD8 and histone modification H3K36me2 in MLL-AF9 transformed acute myeloid leukemia cells (RN2)
2015-12-17 | E-GEOD-71183 | biostudies-arrayexpress
Project description:Integrative epigenomic analysis in MLL-AF9 acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL)
| PRJNA289498 | ENA
Project description:Acute myeloid leukemia (AML) and acute T-lymphoblastic leukemia (T-ALL) maintain the undifferentiated phenotype and proliferative capacity of their respective cells of origin, hematopoietic stem/progenitor cells and immature thymocytes. The mechanisms that maintain these progenitor-like characteristics are poorly understood. We report that transcription factor Zfx is required for the development and propagation of experimental AML caused by MLL-AF9 fusion, and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx activated progenitor-associated gene expression programs and prevented differentiation. Key Zfx target genes included mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescued the propagation of Zfx-deficient AML. These studies identify a common mechanism that controls the cell-of-origin characteristics of acute leukemias derived from disparate lineages and transformation mechanisms. Analysis of genomic ZFX binding in the AML cell line NOMO-1 and the T-ALL cell line RPMI-8402
2014-01-30 | E-GEOD-43147 | biostudies-arrayexpress
Project description:<p>Acute myeloid leukemia (AML) is an aggressive disease with a high relapse rate. In this study, we map the metabolic profile of CD34+(CD38low/-) AML cells and the extracellular vesicle signatures in circulation from AML patients at diagnosis. CD34+ AML cells display high antioxidant glutathione levels and enhanced mitochondrial functionality, both associated with poor clinical outcomes. Although CD34+ AML cells are highly dependent on glucose oxidation and glycolysis for energy, those from intermediate- and adverse-risk patients reveal increased mitochondrial dependence. Extracellular vesicles from AML are mainly enriched in stem cell markers and express antioxidant GPX3, with their profiles showing potential prognostic value. Extracellular vesicles enhance mitochondrial functionality and dependence on CD34+ AML cells via the glutathione/GPX4 axis. Notably, only extracellular vesicles from adverse-risk patients enhance leukemia cell engraftment in vivo. Here, we show a potential noninvasive approach based on liquid ‘cell-extracellular vesicle’ biopsy toward a redefined metabolic stratification in AML.</p><p><br></p><p><strong>Metabolomic analysis on extracellular vesicles</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS11746' rel='noopener noreferrer' target='_blank'><strong>MTBLS11746</strong></a>.</p><p><strong>Lipidomic analysis on extracellular vesicles</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS11523' rel='noopener noreferrer' target='_blank'><strong>MTBLS11523</strong></a>.</p>
2024-12-04 | MTBLS11746 | MetaboLights