Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multiomic characterization of WDR5 WIN site inhibition reveals actionable synergies for MLL-rearranged leukemia

ABSTRACT: In this study, we utilized a multi-omics approach to determine the transcriptional, translational, and proteomic responses to WIN Site inhibition in MLL-rearranged leukemia cells via RNA-Seq, Ribo-Seq, and quantitative proteomics, respectively. We also performed both a whole-genome targeting primary CRISPR screen and a secondary CRISPR screen targeting a currated collection of genes to determine genes important for sensitivity to WIN Site inhibition. These combined data sets rationally guided us in assembling a collection of compounds that, when combined with WIN Site inhibitor, synergistically inhibit growth of MLL-rearranged leukemia cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206931 | GEO | 2023/07/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Proteome alterations in MLL-rearranged leukemia cells following WIN Site inhibition

Project description:WIN Site inhibitors bind the WIN Site of WDR5 resulting in decreased transcription of WDR5 target genes, many of which encode components of the protein synthesis machinery. In this study, we determined proteome alterations in an MLL-rearranged leukemia cell line treated for either 24 or 72 hours with a WIN Site inhibitor. The data from these studies, along with Ribo-Seq, RNA-Seq, and CRISPR screen experiments, guided us in assembling a collection of compounds that, when combined with WIN Site inhibitor, synergistically inhibit growth of MLL-rearranged leukemia cells.

2023-07-04 | PXD035129 | Pride

The WDR5 WIN site interactome

Project description:The WIN site of WDR5 is a druggable pocket that is crucial for WDR5 protein function and carries therapeutic potential for treating cancer. This study evaluates the protein interactions affected by small molecule blockade of the WIN site of WDR5. We find that PDPK1 directly binds the WIN site of WDR5, and we investigate this newfound interaction through proteomic, biochemical, and genomic methods.

2021-01-19 | GSE150400 | GEO

The WDR5 WIN site interactome

Project description:The WDR5 WIN site interactome

| PRJNA631994 | ENA

WIN site inhibition disrupts a subset of WDR5 function

Project description:This study demonstrates the impact of WIN site inhibitors versus WDR5 degradation on H3K4me and transcriptional processes in human Burkitt's lymphoma cells. We use RNA-seq to measure global transcript levels, ChIP-seq to map genomic H3K4me3, and PRO-seq to map genomic polymerase density and primary transcripts. Our data show that WIN site inhibition disables only a specific subset of WDR5 activity, and that H3K4me changes induced by WDR5 depletion do not explain accompanying transcriptional responses.

2022-02-03 | GSE183781 | GEO

Quantitative cellular proteome analysis of Fetal- and Adult-Derived MLL-Rearranged Leukemia

Project description:Infant and adult MLL-rearranged (MLLr) leukemia represents a disease with few treatment options and a dismal prognosis. Here, we present an in-depth proteomic characterization of in utero-initiated and adult-onset MLLr leukemia in a mouse model of MLL-ENL-mediated leukemogenesis. We characterize early proteomic events of MLL-ENL-mediated transformation in fetal and adult progenitors.

2024-04-02 | PXD042249 | Pride

WIN 18,446 2dpp testis culture

Project description:Analysis of 2dpp whole testes cultured for 24h in the presence of WIN 18,446, a BDAD compound. BDADs (Bis-(dichloroacetyl)-diamines) have been shown previously to inhibit spermatogenesis and function as male contraceptives in many species; however, their mechanism of action has yet to be fully described. Results provide insight into the ability of WIN 18,446 to inhibit retinoic acid synthesis in the murine testis. Testes were removed from 2dpp 129 mice and cultured for 24h in an organ culture mold in the presence of WIN 18,446. Total RNA was extracted and hybridized to Affymetrix Mouse Genome 430 2.0 arrays.

2010-11-25 | E-GEOD-25610 | biostudies-arrayexpress

WIN 18,446 2dpp testis culture

2010-11-25 | GSE25610 | GEO

Tet1 plays an essential oncogenic role in MLL-rearranged leukemia

Project description:TET1, the founding member of the TET family of enzymes (TET1/2/3) that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), was first identified as a partner gene in MLL-rearranged leukemia, but its definitive pathological role in leukemia is unclear. The down-regulation of all three TET genes and loss-of-function mutations of TET2 have been frequently observed in various cancers, and it was thought that they all play tumor-suppressor roles in tumorigenesis. Here we show that TET1 is likely a direct target of MLL and significantly up-regulated in MLL-rearranged leukemia, associated with an increased level of 5hmC. Our further in vitro and in vivo studies demonstrate that Tet1 plays an indispensable oncogenic role in MLL-rearranged leukemia, through cooperating with MLL fusion proteins in regulating their co-targets including the Hoxa/Meis1/Pbx3/Flt3 genes. Our data delineate a MLL-fusion/Tet1/Hoxa/Meis1/Pbx3/Flt3 signaling axis in MLL-rearranged leukemia, and highlight TET1 as a potential therapeutic target in treating this presently therapy-resistant disease.

2015-12-14 | GSE42990 | GEO

Tet1 plays an essential oncogenic role in MLL-rearranged leukemia

2015-12-14 | E-GEOD-42990 | biostudies-arrayexpress

MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia

Project description:In this study, we identify MBNL1 as a unique molecular vulnerability across MLL-rearranged leukemias. Through transcriptomic profiling and novel splicing analyses of MLL-rearranged leukemia cell lines following shRNA knockdown of MBNL1, we show that MBNL1 regulates alternative splicing (predominantly intron retention) of genes essential to MLL-rearranged leukemogenesis, such as DOT1L and SETD1A.

2020-03-25 | GSE123441 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data