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Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8 21)-positive Acute Myeloid Leukemia

ABSTRACT: Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8 21)-positive Acute Myeloid Leukemia

PROVIDER: PRJNA896958 | ENA |

REPOSITORIES: ENA

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Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8 21)-positive Acute Myeloid Leukemia [CUT&RUN]

Project description:Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8 21)-positive Acute Myeloid Leukemia [CUT&RUN]

| PRJNA896960 | ENA

Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8 21)-positive Acute Myeloid Leukemia [RNA-seq]

Project description:Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8 21)-positive Acute Myeloid Leukemia [RNA-seq]

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Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8 21)-positive Acute Myeloid Leukemia [ATAC-seq]

Project description:Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8 21)-positive Acute Myeloid Leukemia [ATAC-seq]

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HDAC3 preferentially binds to RUNX1 in t(8;21) AML cells and collaborates with RUNX1 to repress AML1-ETO-mediated transcriptional activation

Project description:Human histone deacetylase 3 (HDAC3) plays an important role in gene transcription in diseased human cells, such as leukemia. The t(8;21) chromosomal translocation is one of the most commonly observed genetic abnormalities associated with acute myeloid leukemia. This translocation generates the AML1-ETO fusion protein between the wild-type RUNX1 transcription factor and wild-type ETO transcriptional corepressor. To better understand the role of HDAC3 in t(8;21) leukemogenesis, the human HDAC3-containing complexes were isolated from stably-transfected HeLa cells by using anti-FLAG immunoprecipitation. The resulting complexes were resolved in SDS-PAGE. The components of the complexes were identified using LC-MS/MS. We report here that the human RUNX1 transcription is a component of the HDAC3 complexes. We demonstrate that HDAC3 and RUNX1 collaboratively repress AML1-ETO-mediated transcription. These results reveal new insight into how AML1-ETO, RUNX1, and HDAC3 crosstalk to deregulate gene transcription in t(8;21) leukemia cells.

2020-02-17 | PXD017230 | Pride

SWATH-MS Proteomic Analysis Identifies C/EBPβ Suppression by RUNX1-ETO as a Potential Mediator of Block in Differentiation

Project description:Acute myeloid leukemia (AML) is a heterogenous disease with multiple morphological, immunophenotypic and genetic features. The t(8;21), which results in the expression of RUNX1-ETO (aka AML1-ETO), is accountable for 12% of AML cases (1). Previously, this fusion protein has been shown to block hematopoietic development of normal human hematopoietic stem and progenitor cells (HSPC), as well as promoting the cells’ self-renewal potential (2,3). Even though several studies have determined the transcriptomic changes observed in cells expressing RUNX1-ETO, there is a paucity of studies quantitating proteomic changes. Given that transcriptional regulation is likely mediated by changes in transcription factor (TF) expression, I hypothesize that RUNX1-ETO leads to TF dysregulation, of which critical components might dictate differentiation blockage.

2026-07-06 | PXD046908 | Pride

Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8;21)-positive Acute Myeloid Leukemia [CUT&RUN]

Project description:To investigate the therapeutic potential of targeting RUNX1/ETO with lipid nanoparticles encapsulating chemically modefied siRNA. Epegnomic profiling was performing on cells lines after lipid nanoparticles in vitro.

2022-11-09 | GSE217110 | GEO

Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8;21)-positive Acute Myeloid Leukemia [ATAC-seq]

Project description:To investigate the therapeutic potential of targeting RUNX1/ETO with lipid nanoparticles encapsulating chemically modefied siRNA. Chromatin Accessibility (ATAC-seq) was performing on cells lines after lipid nanoparticles in vitro.

2022-11-09 | GSE217112 | GEO

Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8;21)-positive Acute Myeloid Leukemia [RNA-seq]

Project description:To investigate the therapeutic potential of targeting RUNX1/ETO with lipid nanoparticles encapsulating chemically modefied siRNA. Gene expression profiling was performing on cells lines after lipid nanoparticles in vitro and on harvested cells from treated mice in vivo.

2022-11-09 | GSE217109 | GEO

The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle regulation to Drive Leukemic Transformation [ChIP]

Project description:Oncogenic transcription factors such as the leukaemic fusion protein RUNX1/ETO constitute cancer-specific but highly challenging therapeutic targets, whose functions depend on pharmacologically tractable downstream pathways. Here we interrogated the transcriptional network of RUNX1/ETO in an in vitro/in vivo RNAi screen and identified Cyclin D2 (CCND2) as a crucial transmitter of RUNX1/ETO-driven leukemic propagation. RUNX1/ETO drives CCND2 expression by binding to a regulatory element upstream of the CCND2 promoter. Both knockdown of CCND2 and treatment with the CDK4/6 inhibitor palbociclib inhibited leukemic expansion patient-derived AML cells and impaired engraftment of immunodeficient murine hosts. Our data demonstrate that RUNX1/ETO drives leukaemia by directly promoting cell cycle progression and establish inhibition of G1 CCND-CDK complexes as a promising therapeutic strategy for RUNX1/ETO-driven AML.

2019-04-12 | GSE117105 | GEO