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Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [RNASeq_Cdx2_4weekspost_Tamoxifen]

ABSTRACT: Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [RNASeq_Cdx2_4weekspost_Tamoxifen]

PROVIDER: PRJNA552223 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9624770.fastq.gz	Fastqsanger.gz
	SRR9624771.fastq.gz	Fastqsanger.gz
	SRR9624772.fastq.gz	Fastqsanger.gz
	SRR9624773.fastq.gz	Fastqsanger.gz
	SRR9624774.fastq.gz	Fastqsanger.gz

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Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia

Project description:Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia

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Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [RNASeq_Cdx2_secondaryAML]

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Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [Chip-Seq]

Project description:Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [Chip-Seq]

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Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [RNASeq_Cdx2_secondaryAML]

Project description:The caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs . Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations.

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Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [RNASeq_Cdx2_4weekspost_Tamoxifen]

Project description:The caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs. Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations.

2019-09-30 | GSE133679 | GEO

Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [Chip-Seq]

Project description:The caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs. Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations.

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Hematopoietic stem and progenitor cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia.

Project description:The caudal-related homeobox transcription factor CDX2 is expressed in leukemic cells but not during normal blood formation. Retroviral overexpression of Cdx2 induces AML in mice, however the developmental stage at which CDX2 exerts its effect is unknown. We developed a conditionally inducible Cdx2 mouse model to determine the effects of in vivo, inducible Cdx2 expression in hematopoietic stem and progenitor cells (HSPCs). Cdx2-transgenic mice develop myelodysplastic syndrome with progression to acute leukemia associated with acquisition of additional driver mutations. Cdx2-expressing HSPCs demonstrate enrichment of hematopoietic-specific enhancers associated with pro-differentiation transcription factors. Furthermore, treatment of Cdx2 AML with azacitidine decreases leukemic burden. Extended scheduling of low-dose azacitidine shows greater efficacy in comparison to intermittent higher-dose azacitidine, linked to more specific epigenetic modulation. Conditional Cdx2 expression in HSPCs is an inducible model of de novo leukemic transformation and can be used to optimize treatment in high-risk AML.

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Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia

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

2019-09-30 | GSE133829 | GEO

CDX2 ChIP-seq

Project description:Somatic DNA alteration underlies tumor development and progression, and gives rise to tumors with diverse genetic contexts. Here, we identify in a collection of 29 colorectal cancer cell lines and 226 primary colorectal tumors recurrent amplification of chromosome 13, an alteration highly restricted to colorectal-derived cancers. A minimal region of amplification on 13q12.2 pinpoints caudal type homeobox transcription factor CDX2, a master regulator of anterior-posterior patterning, midgut development, and intestinal epithelial cell differentiation and maintenance. In contrast to its described role as a colorectal tumor suppressor, we show that in the context of genomic amplification, CDX2 is required for proliferation and anchorage-independent growth of colorectal cancer cells. By genome-wide expression and location analysis, we reveal that CDX2 directly promotes expression of Wnt pathway genes. Further results suggest that CDX2 induces expression of intestinal differentiation markers and modulates Î²-catenin transcriptional activity. These data characterize CDX2 as a novel lineage-survival oncogene deregulated in colorectal cancer. ChIP-seq analysis of CDX2 binding sites in COLO320 cells

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