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IDENTIFICATION AND FUNCTIONAL DEMONSTRATION OF A FETAL-SPECIFIC AXIS THAT POTENTLY SUPPRESSES MLL-FUSION DRIVEN MURINE AML

ABSTRACT: IDENTIFICATION AND FUNCTIONAL DEMONSTRATION OF A FETAL-SPECIFIC AXIS THAT POTENTLY SUPPRESSES MLL-FUSION DRIVEN MURINE AML

PROVIDER: PRJNA828262 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18825356.fastq.gz	Fastqsanger.gz
	SRR18825357.fastq.gz	Fastqsanger.gz
	SRR18825358.fastq.gz	Fastqsanger.gz
	SRR18825359.fastq.gz	Fastqsanger.gz

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IDENTIFICATION AND FUNCTIONAL DEMONSTRATION OF A FETAL-SPECIFIC AXIS THAT POTENTLY SUPPRESSES MLL-FUSION DRIVEN MURINE AML

Project description:MLL-rearrangements (MLL-r) are recurrent genetic events in acute myeloid leukemia (AML) and frequently associate with poor prognosis. In infants, MLL-r have been suggested to be sufficient to drive transformation. However, despite the prenatal origin of MLL-r, the incidence of congenital leukemia is very low with transformation usually occurring postnatally. The influence of prenatal signals on leukemogenesis, such as those mediated by the fetal-specific RNA binding protein LIN28B, remains controversial. Here, using a dual-transgenic mouse model that co-express MLL-ENL and LIN28B, we investigated the impact of LIN28B on AML. We show that LIN28B impedes the progression of MLL-r AML through a compromised leukemia initiating cell activity and a suppression of MYB signaling. Mechanistically, rather than involving the well-studied Lin28B-let7 miR axis, we found that LIN28B directly bound MYBBP1A mRNA, a co-repressor of MYB, and that positively correlated with MYBBP1A protein levels. Overexpression of MYBBP1A in MLL-ENL driven leukemogenesis largely phenocopied the tumor suppressor effects of LIN28B. Thereby, our work proposes that the developmentally-restricted expression of LIN28B during fetal development provides a protection against MYB-dependent AML.

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IDENTIFICATION AND FUNCTIONAL DEMONSTRATION OF A FETAL-SPECIFIC AXIS THAT POTENTLY SUPPRESSES MLL-FUSION DRIVEN MURINE AML miRNA-seq [WT vs ME]

Project description:IDENTIFICATION AND FUNCTIONAL DEMONSTRATION OF A FETAL-SPECIFIC AXIS THAT POTENTLY SUPPRESSES MLL-FUSION DRIVEN MURINE AML miRNA-seq [WT vs ME]

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IDENTIFICATION AND FUNCTIONAL DEMONSTRATION OF A FETAL-SPECIFIC AXIS THAT POTENTLY SUPPRESSES MLL-FUSION DRIVEN MURINE AML RNA-seq [L28BME vs ME]

Project description:IDENTIFICATION AND FUNCTIONAL DEMONSTRATION OF A FETAL-SPECIFIC AXIS THAT POTENTLY SUPPRESSES MLL-FUSION DRIVEN MURINE AML RNA-seq [L28BME vs ME]

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IDENTIFICATION AND FUNCTIONAL DEMONSTRATION OF A FETAL-SPECIFIC AXIS THAT POTENTLY SUPPRESSES MLL-FUSION DRIVEN MURINE AML miRNA-seq [L28BME vs ME]

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IDENTIFICATION AND FUNCTIONAL DEMONSTRATION OF A FETAL-SPECIFIC AXIS THAT POTENTLY SUPPRESSES MLL-FUSION DRIVEN MURINE AML RNA-seq [L28BME vs ME]

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