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Novel Inhibitors of the Histone-Methyltransferase DOT1L Show Potent Antileukemic Activity in Patient-derived Xenografts (RNA-seq dataset)

ABSTRACT: Novel Inhibitors of the Histone-Methyltransferase DOT1L Show Potent Antileukemic Activity in Patient-derived Xenografts (RNA-seq dataset)

PROVIDER: PRJNA627611 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11595449.fastq.gz	Fastqsanger.gz
	SRR11595450.fastq.gz	Fastqsanger.gz
	SRR11595451.fastq.gz	Fastqsanger.gz
	SRR11595452.fastq.gz	Fastqsanger.gz
	SRR11595453.fastq.gz	Fastqsanger.gz

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Novel Inhibitors of the Histone-Methyltransferase DOT1L Show Potent Antileukemic Activity in Patient-derived Xenografts

Project description:Novel Inhibitors of the Histone-Methyltransferase DOT1L Show Potent Antileukemic Activity in Patient-derived Xenografts

| PRJNA627609 | ENA

Novel Inhibitors of the Histone-Methyltransferase DOT1L Show Potent Antileukemic Activity in Patient-derived Xenografts (ChIP-seq dataset)

Project description:Novel Inhibitors of the Histone-Methyltransferase DOT1L Show Potent Antileukemic Activity in Patient-derived Xenografts (ChIP-seq dataset)

| PRJNA627612 | ENA

Novel Inhibitors of the Histone-Methyltransferase DOT1L Show Potent Antileukemic Activity in Patient-derived Xenografts (ChIP-seq dataset)

Project description:using ChIP-seq we examined Chromatin occupancy of the MLL-fusion complex members Menin and DOT1L after treatment with DOT1L methyltransferase inhibitors EPZ5676 and the novel compounds "compound 10" and "compound 11" as well as with the Menin-inhibitor VTP50469 in MOLM13 cells. Furthermore we used ChiP-seq to quantify the loss of H3K79me2 (histone mark deposited by DOT1L) after treatment with the DOT1L inhibitors EPZ5676 and "compound 10" in MOLM13 and RS4,11 cells.

2020-06-01 | GSE149183 | GEO

Novel Inhibitors of the Histone-Methyltransferase DOT1L Show Potent Antileukemic Activity in Patient-derived Xenografts (RNA-seq dataset)

Project description:Using 3-end RNA-seq followed by digital gene expression analyses we assessed genes that change expression upon treatment with the DOT1L-methyltransferase inhibitors EPZ5676 and the novel drug "compound 10"

2020-06-01 | GSE149184 | GEO

Novel Inhibitors of the Histone-Methyltransferase DOT1L Show Potent Antileukemic Activity in Patient-derived Xenografts

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

2020-06-01 | GSE149185 | GEO

Expression Profiling of Mixed Lineage Leukemia Cells Treated with a Potent Small-Molecule DOT1L Inhibitor

Project description:Cell lines bearing MLL translocations (MV4-11 and MOLM-13) were treated with a potent, selective inhibitor of the DOT1L histone methyl transferase. Treatment of MLL-rearranged cell lines with the DOT1L inhibitor selectively inhibits H3K79 methylation and blocks expression of leukemogenic genes. Here we provide expression profiling data of cells treated with DOT1L inhibitor or vehicle control. MV4-11 cells were treated with 3 uM EPZ004777 (DOT1L inhibitor) or vehicle control (0.1% DMSO) for 2, 4 and 6 days. MOLM-13 cells were treated with 3 uM EPZ004777 (DOT1L inhibitor) or vehicle control (0.1% DMSO) for 6 days. For each unique conditon, 3 biological replicates were generated for expression profiling.

2011-07-11 | E-GEOD-29828 | biostudies-arrayexpress

Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia

Project description:Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia

| PRJNA914332 | ENA

Expression Profiling of Mixed Lineage Leukemia Cells Treated with a Potent Small-Molecule DOT1L Inhibitor

2011-07-11 | GSE29828 | GEO

Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia

Project description:We identified novel nicotinamide-based FLT3 inhibitors ( HSN748) that specifically target FLT3-ITD at sub-nanomolar concentrations and are effective against drug-resistant secondary mutations. In the current study, we evaluated these compounds’ antileukemic activity against FLT3-ITD and gatekeeper mutations in drug-resistant AML, relapsed/refractory AMLs with FLT3 mutations

2024-06-15 | GSE221459 | GEO

DOT1L regulates pericentromeric heterochromatin

Project description:Many repetitive DNA elements are packaged in heterochromatin, but depend on occasional transcription to maintain long-term silencing. The factors that promote transcription of repeat elements in heterochromatin are largely unknown. Here, we show that DOT1L, a histone methyltransferase that modifies lysine 79 of histone H3 (H3K79), is required for transcription of major satellite repeats to maintain pericentromeric heterochromatin (PCH), and that this function is essential for preimplantation development. DOT1L is a transcriptional activator at single-copy genes but does not have a known role in repeat element transcription. We show that H3K79me3 is specifically enriched at repetitive elements, that loss of DOT1L compromises pericentromeric major satellite transcription, and that this function depends on interaction between DOT1L and the chromatin remodeler SMARCA5. DOT1L inhibition causes chromosome breaks and cell cycle defects, and leads to embryonic lethality. Together, our findings uncover a vital new role for DOT1L in transcriptional activation of heterochromatic repeats.

2023-05-26 | PXD028824 | Pride

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