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T-cell ALL in response to TAL1-KD, UTX-KD, and GSKJ4 treatment

ABSTRACT: T-cell ALL in response to TAL1-KD, UTX-KD, and GSKJ4 treatment

PROVIDER: PRJNA293693 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1748013.fastq.gz	Fastqsanger.gz
	SRR1748014_1.fastq.gz	Fastqsanger.gz
	SRR1748014_2.fastq.gz	Fastqsanger.gz
	SRR1748015_1.fastq.gz	Fastqsanger.gz
	SRR1748015_2.fastq.gz	Fastqsanger.gz

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Gene expression in TAL1-driven T-cell ALL in response to TAL1-KD, UTX-KD, and GSKJ4 treatment

Project description:T-cell Acute Lymphoblastic Leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities, gene expression signatures and prognoses. However, it remains unclear whether T-ALL subtypes differ at the functional level, and as such T-ALL treatments are uniformly applied across subtypes leading to variable responses between patients. Here we reveal the existence of a subtype-specific epigenetic vulnerability in T-ALL whereby a particular subgroup of T-ALL characterized by expression of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in dosage and activity of the histone 3 lysine 27 (H3K27) demethylase UTX. Specifically, we identify UTX as a co-activator of TAL1. Furthermore, we demonstrate that UTX, previously described as a tumor suppressor in T-ALL, is in fact a potent oncogene essential for maintaining the leukemic phenotype of TAL1-positive (but not TAL1-negative) T-ALL. Exploiting this subtype-specific epigenetic vulnerability, we designed a novel therapeutic approach based on UTX inhibition through in vivo administration of an H3K27 demethylase inhibitor that is highly effective against TAL1-positive primary human leukemia. These findings provide the first opportunity to develop personalized epigenetic therapy for T-ALL patients.

2016-02-01 | GSE72299 | GEO

H3K27 methylation changes in Jurkat cells in response to TAL1-KD

2016-02-01 | GSE72298 | GEO

UTX inhibition as selective epigenetic therapy against TAL1-driven T cell acute lymphoblastic leukemia

Project description:We performed ChIP-Seq in Jurkat T-ALL cells to identify UTX binding sites across the genome. We then compared UTX binding sites (this study) with TAL1 binding sites (Data from Palii, 2011 GSE25000), and found a high degree of overlap between TAL1 and UTX in Jurkat T-All cells. Indeed, over 80% of TAL1 binding sites overlap with UTX.

2016-02-01 | GSE64832 | GEO

T-cell ALL in response to TAL1-KD, UTX-KD, and GSKJ4 treatment

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

2016-02-01 | GSE72300 | GEO

Homo sapiens

Project description:Gene expression in TAL1-driven T-cell ALL in response to TAL1-KD, UTX-KD, and GSKJ4 treatment

| PRJNA293697 | ENA

Expression data from human HSPC with O/E TAL1 or KD/TAL1

Project description:Analyses of the consequences of up- and down-regulating SCL/TAL1 in human enriched hematopoietic stem progenitor cells (HSPCs). We used microarrays to detail the global gene expression program of human cord blood HSPCs (CD34+CD38-lowCD34RA-CD90+) in which SCL/TAL1 expression is either up- or down-regulated.

2015-10-23 | GSE62634 | GEO

TAL1 knock down in human erythroid progenitors

Project description:We used microarray profiling in erythroid cells to uncover TAL1 dependent genes in a hematopoietic differentiation context. Differentiated ex vivo hematopoietic multipotential progenitors isolated from adult peripheral blood. The knockdown of TAL1 (KD) was induced in pro-erythroblasts (Days 8 and 9 of differentiation) using lentivirus-delivered shRNA. A scramble (scr) shRNA sequence was used as a negative control.

2010-12-14 | E-GEOD-20545 | biostudies-arrayexpress

Utx interactome in mouse myeloid progenitor cells

Project description:Immunoprecipitation of Utx followed by mass spectrometry analysis to identify Utx binding partners in mouse myeloid progenitor cells.

2018-04-30 | PXD005011 | Pride

Alternative mRNA splicing controls functions of the human H3K27 demethylase UTX/KDM6A

Project description:The UTX/KDM6A gene encodes the UTX histone H3K27 demethylase, which plays an important role in mammalian development and is frequently mutated in cancers and particularly, in urothelial cancers. Using BioID technique, we explored the interactome of different UTX isoforms.

2024-01-28 | PXD041254 | Pride

TAL1 knock down in Jurkat cells

Project description:We used microarray profiling in Jurkat cells to uncover TAL1 dependent genes in a leukemic context. Clonal Jurkat lines expressing a Doxycycline (Dox) -inducible shRNA against TAL1 coding sequence were generated. A clone in which Dox treatment led to 80% decrease of TAL1 mRNA was chosen.

2010-12-14 | E-GEOD-20544 | biostudies-arrayexpress

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