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Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia

ABSTRACT: Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia

PROVIDER: PRJNA787920 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17196831_1.fastq.gz	Fastqsanger.gz
	SRR17196831_2.fastq.gz	Fastqsanger.gz
	SRR17196832_1.fastq.gz	Fastqsanger.gz
	SRR17196832_2.fastq.gz	Fastqsanger.gz
	SRR17196833_1.fastq.gz	Fastqsanger.gz

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Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia (RNA-Seq)

Project description:Detailed genomic and epigenomic analyses of MECOM (the MDS1 and EVI1 complex locus) have revealed that inversion or translocation of chromosome 3 at MECOM drive inv(3)/t(3;3) myeloid leukemias and revealed MECOM germline mutations in patients with MECOM-associated bone marrow failure syndromes. Here we identify a novel, previously unannotated oncogenic RNA-splicing derived isoform of EVI1 which is frequently present in inv(3)/t(3;3) AML and directly contributes to leukemic transformation. Expression of this EVI1 splice variant enhanced the self-renewal of hematopoietic stem cells and introduction of mutant SF3B1 in mice bearing the humanized inv(3)(q21;26) allele hastened leukemogenesis in vivo. These data provide a mechanistic basis for the frequent co-occurrence of SF3B1 mutations as well as new insights into the pathogenesis of myeloid leukemias harboring inv(3)/t(3;3).

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