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Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2 [RNA-seq]

ABSTRACT: Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2 [RNA-seq]

PROVIDER: PRJNA1019250 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26124549_1.fastq.gz	Fastqsanger.gz
	SRR26124549_2.fastq.gz	Fastqsanger.gz
	SRR26124550_1.fastq.gz	Fastqsanger.gz
	SRR26124550_2.fastq.gz	Fastqsanger.gz
	SRR26124551_1.fastq.gz	Fastqsanger.gz

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Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2

Project description:Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2

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Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2 [ChIP-Seq]

Project description:Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2 [ChIP-Seq]

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Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2

Project description:Acute myeloid leukemia (AML) driven by the activation of EVI1 due to chromosome 3q26/MECOM rearrangements is incurable with current chemotherapy regimens. Insight into the mechanism by which EVI1 drives myeloid transformation is needed to target EVI1 in those leukemias. Here we demonstrate recurrent interaction of CTBP1/2 with a unique PLDLS motif in EVI1, which is indispensable for leukemic transformation of 3q26/MECOM rearranged AML. A PLDLS competitor construct outcompetes EVI1 to CTBP1/2 binding and inhibits AML proliferation in xenotransplant models. This proof-of-concept study opens the possibility to target one of the most incurable forms of AML using specific inhibitors directed to EVI1/CTBP1/2 interaction. Our findings have important implications for other tumour types with aberrant expression of EVI1 or other oncogenic transcription factors that also depend on CTBP1/2 interaction.

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Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2

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Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2 [ChIP-Seq]

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Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2 [RNA-seq]

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Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2

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

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Chromatin interactions of the EVI1 oncogene in myeloid leukaemia (4C-Seq)

Project description:EVI1 expression is associated with poor prognosis in myeloid leukaemia. Aberrant expression can result from Chr.3q alterations, which cause juxtaposition of enhancers that induce EVI1 activation via long-range chromatin interactions. More often, however, EVI1 expression occurs unrelated to 3q alterations, and it is unclear if its expression underlies similar dependencies as 3q+ cells. As enhancers regulate promoters by physical interaction/chromatin looping, we explored if the EVI1 promoter in EVI1+3q- cells interacts with distally located chromatin and if these intereactions promote EVI1 expression.

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Chromatin interactions of the EVI1 oncogene in myeloid leukaemia (ChIP-Seq)

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Chromatin interactions of the EVI1 oncogene in myeloid leukaemia (ATAC-Seq)

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