MiR196b-/- DNMT3A-mutant AML [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA792547 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:R848 treated DNMT3A-mutant AML [RNA-seq]
| PRJNA704972 | ENA
Project description:microRNA (miRNA or miR) are aberrantly expressed in acute myeloid leukemia (AML), and clinically may have diagnostic, prognostic, and therapeutic value. We identify miR-196b, is overexpressed in high-risk subset of DNMT3A-mutant AML and its activity is important to maintain a differentiation block and limit innate immune signaling pathways in AML. We interrogated previously published experimentally defined and computationally predicated miR-196b targets compared with genes differentially expressed in miR-196b-/-Dnmt3a/Flt3ITD AML versus Dnmt3a/Flt3ITD AML. This identified that miR-196b regulates Pou2f1 and Pou2f2 (Oct1 and Oct2) in Dnmt3a/Flt3-mutant AML.
2024-09-01 | GSE192639 | GEO
Project description:microRNA in DNMT3A-mutant AML [miRNA-Seq]
| PRJNA707795 | ENA
Project description:microRNA (miRNA or miR) are aberrantly expressed in acute myeloid leukemia (AML), and clinically may have diagnostic, prognostic, and therapeutic value. We identify miR-196b, is overexpressed in high-risk subset of DNMT3A-mutant AML and its activity is important to maintain a differentiation block and limit innate immune signaling pathways in AML. We interrogated previously published experimentally defined and computationally predicated miR-196b targets demonstrating that miR-196b regulates Toll-like Receptor Signaling. This work uncovered that miR-196b represses TLR7/8 activation and innate immune signaling in AML and that TLR7/8 activates a Stat1 transcriptional response associated with induced co-stimulatory molecule expression on the surface of AML-derived monocytes and dendritic-like cells.
2022-07-31 | GSE167571 | GEO
Project description:Acute myeloid leukemia (AML) is a fatal hematological malignancy for most patients, and DNA methyltransferase 3A (DNMT3A) mutations occur in about 30-35% of AML patients. We show graphdiyne oxide (GDYO), a member of two-dimensional carbon nanomaterials3, demonstrates an anti-leukemia effect in vitro and in vivo against AML cells with DNMT3A mutation specifically. Here, we used RNA-seq to depict transcriptome of AML cells with or without GDYO treatment.
2022-08-23 | GSE190871 | GEO
Project description:microRNA (miRNA or miR) are aberrantly expressed in acute myeloid leukemia (AML), and clinically may have diagnostic, prognostic, and therapeutic value. We identify miR-196b, is overexpressed in high-risk subset of DNMT3A-mutant AML and its activity is important to maintain a differentiation block and limit innate immune signaling pathways in AML. We interrogated previously published experimentally defined and computationally predicated miR-196b targets demonstrating that miR-196b regulates Toll-like Receptor Signaling. This work uncovered that miR-196b represses TLR7/8 activation and innate immune signaling in AML and that TLR7/8 activates a Stat1 transcriptional response associated with induced co-stimulatory molecule expression on the surface of AML-derived monocytes and dendritic-like cells.
2022-07-31 | GSE168509 | GEO
Project description:Cytogenetically normal acute myeloid leukemia (CN-AML) represents nearly 50% of human acute myeloid leukemia (AML) cases with a 5-year overall survival of approximately 30%. In CN-AML with poorer prognosis, mutations in the de novo DNA methyltransferase (DNMT3A) and the FMS-like tyrosine kinase 3 (Flt3) commonly co-occur (1-3). We demonstrate that mice with Flt3-internal-tandem duplication (Flt3ITD) and inducible deletion of Dnmt3a spontaneously develop a rapidly-lethal, completely-penetrant, and transplantable AML of normal karyotype. These murine AML retain a single Dnmt3a floxed allele, revealing the oncogenic potential of Dnmt3a haploinsufficiency. FLT3-ITD/DNMT3A-mutant primary human and murine AML demonstrate a similar pattern of global DNA methylation. In the murine model, rescuing DNMT3A expression was accompanied by DNA re-methylation and loss of clonogenic potential, suggesting that Dnmt3a-mutant oncogenic effects are reversible. Differentially methylated genomic regions were associated with changes in the expression of nearby genes. Moreover, dissection of the cellular architecture of the AML model using single-cell RNA-Seq, flow cytometry and colony assays identified clonogenic subpopulations that differentially express genes that are sensitive to the methylation of nearby genomic loci and varied in response to Dnmt3a levels. Thus, Dnmt3a haploinsufficiency transforms Flt3ITD myeloproliferative disease by modulating methylation-sensitive gene expression within a clonogenic AML subpopulation. To identify the gene expression changes associated with Dnmt3a loss of function in human and murine Flt3-ITD and Dnmt3a-mutant AML (Bulk RNA-Seq).
2016-03-27 | E-GEOD-77846 | biostudies-arrayexpress
Project description:Cytogenetically normal acute myeloid leukemia (CN-AML) represents nearly 50% of human acute myeloid leukemia (AML) cases with a 5-year overall survival of approximately 30%. In CN-AML with poorer prognosis, mutations in the de novo DNA methyltransferase (DNMT3A) and the FMS-like tyrosine kinase 3 (Flt3) commonly co-occur (1-3). We demonstrate that mice with Flt3-internal-tandem duplication (Flt3ITD) and inducible deletion of Dnmt3a spontaneously develop a rapidly-lethal, completely-penetrant, and transplantable AML of normal karyotype. These murine AML retain a single Dnmt3a floxed allele, revealing the oncogenic potential of Dnmt3a haploinsufficiency. FLT3-ITD/DNMT3A-mutant primary human and murine AML demonstrate a similar pattern of global DNA methylation. In the murine model, rescuing DNMT3A expression was accompanied by DNA re-methylation and loss of clonogenic potential, suggesting that Dnmt3a-mutant oncogenic effects are reversible. Differentially methylated genomic regions were associated with changes in the expression of nearby genes. Moreover, dissection of the cellular architecture of the AML model using single-cell RNA-Seq, flow cytometry and colony assays identified clonogenic subpopulations that differentially express genes that are sensitive to the methylation of nearby genomic loci and varied in response to Dnmt3a levels. Thus, Dnmt3a haploinsufficiency transforms Flt3ITD myeloproliferative disease by modulating methylation-sensitive gene expression within a clonogenic AML subpopulation. To identify the gene expression changes associated with Dnmt3a loss of function in human and murine Flt3-ITD and Dnmt3a-mutant AML (Single Cell RNA-Seq).
2016-03-27 | E-GEOD-77847 | biostudies-arrayexpress
Project description:Graphdiyne oxide nanosheets display anti-leukemia efficacy specifically against DNMT3A-mutant AML cells [RNA-Seq]
| PRJNA788781 | ENA
Project description:RNA-seq of JAK2VF and DNMT3A mutant Myelofibrosis patients
| PRJEB28858 | ENA