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Links from GEO DataSets

Items: 20

1.

A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing
Platforms:
GPL24676 GPL18573
35 Samples
Download data: BW
Series
Accession:
GSE150555
ID:
200150555
2.

A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models[RNA-seq]

(Submitter supplied) Biochemical interactions between WD40 repeat domain protein 5 (WDR5) and its various cellular partners such as Mixed Lineage Leukemia (MLL) and c-MYC are essential for sustaining oncogenesis in a range of human cancers. Thus, small molecules targeting WDR5 represent an attractive strategy for anti-cancer interventions. However, currently available inhibitors designed to interfere with WDR5 binding to a specific partner (such as OICR-9429 that blocks WDR5-MLL interaction) show a promising but rather partial therapeutic effect, presumably due to incomplete blockade of WDR5 functionality and interactions with various partners. more...
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing
Platforms:
GPL18573 GPL24676
26 Samples
Download data: XLS
3.

A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models [ChIP-seq]

(Submitter supplied) Biochemical interactions between WD40 repeat domain protein 5 (WDR5) and its various cellular partners such as Mixed Lineage Leukemia (MLL) and c-MYC are essential for sustaining oncogenesis in a range of human cancers. Thus, small molecules targeting WDR5 represent an attractive strategy for anti-cancer interventions. However, currently available inhibitors designed to interfere with WDR5 binding to a specific partner (such as OICR-9429 that blocks WDR5-MLL interaction) show a promising but rather partial therapeutic effect, presumably due to incomplete blockade of WDR5 functionality and interactions with various partners. more...
Organism:
Homo sapiens
Type:
Genome binding/occupancy profiling by high throughput sequencing
Platform:
GPL18573
9 Samples
Download data: BW
Series
Accession:
GSE150552
ID:
200150552
4.

Discovery of a dual PROTAC for degrading WDR5 and Ikaros oncoproteins as therapeutics [GRO-Seq]

(Submitter supplied) WD repeat domain 5 (WDR5), a chromatin regulator associated with MLL complex and MYC oncoproteins, was shown to be critical for oncogenesis in human cancers and represents an attractive drug target. Inhibitors for targeting protein-protein interaction interfaces (PPIs) within WDR5 were developed; however, they inhibited only a part of WDR5-mediated functional interactions, exerting rather limited antitumor effects. more...
Organism:
Homo sapiens
Type:
Other
Platform:
GPL21290
4 Samples
Download data: BW
Series
Accession:
GSE195729
ID:
200195729
5.

Discovery of a dual PROTAC for degrading WDR5 and Ikaros oncoproteins as therapeutics

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.
Organism:
Homo sapiens; Drosophila melanogaster
Type:
Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing
4 related Platforms
22 Samples
Download data: BW
Series
Accession:
GSE175548
ID:
200175548
6.

Discovery of a dual PROTAC for degrading WDR5 and Ikaros oncoproteins as therapeutics [RNA-Seq]

(Submitter supplied) WD repeat domain 5 (WDR5), a chromatin regulator associated with MLL complex and MYC oncoproteins, was shown to be critical for oncogenesis in human cancers and represents an attractive drug target. Inhibitors for targeting protein-protein interaction interfaces (PPIs) within WDR5 were developed; however, they inhibited only a part of WDR5-mediated functional interactions, exerting rather limited antitumor effects. more...
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing
Platforms:
GPL18573 GPL24676
12 Samples
Download data: XLSX
7.

Discovery of a dual PROTAC for degrading WDR5 and Ikaros oncoproteins as therapeutics [ChIP-Seq]

(Submitter supplied) WD repeat domain 5 (WDR5), a chromatin regulator associated with MLL complex and MYC oncoproteins, was shown to be critical for oncogenesis in human cancers and represents an attractive drug target. Inhibitors for targeting protein-protein interaction interfaces (PPIs) within WDR5 were developed; however, they inhibited only a part of WDR5-mediated functional interactions, exerting rather limited antitumor effects. more...
Organism:
Drosophila melanogaster; Homo sapiens
Type:
Genome binding/occupancy profiling by high throughput sequencing
Platform:
GPL22339
6 Samples
Download data: BW
Series
Accession:
GSE175544
ID:
200175544
8.

Structure-Based Discovery of Potent WD Repeat Domain 5 Inhibitors that Demonstrate Efficacy and Safety in Preclinical Animal Models

(Submitter supplied) WD repeat domain 5 (WDR5) is a core scaffolding component of many multi-protein complexes that perform a variety of critical chromatin-centric processes in the nucleus. WDR5 is component of the mixed lineage leukemia MLL/SET complex and localizes MYC to chromatin tumor-critical target genes. Overexpression of WDR5 promotes oncogenesis in a variety of human cancers that are often associated with poor prognoses. more...
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing
Platform:
GPL24676
12 Samples
Download data: TXT
Series
Accession:
GSE203101
ID:
200203101
9.

Expression changes after Inhibition of AHD in Molm-13 cells

(Submitter supplied) Formation of AF9/ENL/AF4/AFF4-containing super elongation complexes (SEC) and catalytic activity of DOT1L are required for MLL-rearranged leukemia. We evaluated gene expression changes after inhibition of AHD in leukemia cells.
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing
Platform:
GPL24676
6 Samples
Download data: XLSX
10.

The histone H2B ubiquitin ligase RNF20 is required for MLL-rearranged leukemia

(Submitter supplied) MLL-fusions are potent oncogenes that initiate aggressive forms of acute leukemia. As aberrant transcriptional regulators, MLL-fusion proteins alter gene expression in hematopoietic cells through interactions with the histone H3 lysine 79 (H3K79) methyltransferase DOT1L. Notably, interference with MLL-fusion cofactors like DOT1L is an emerging therapeutic strategy in this disease. Here we identify the histone H2B E3 ubiquitin ligase RNF20 as an additional requirement for MLL-fusion-mediated leukemogenesis. more...
Organism:
Mus musculus
Type:
Expression profiling by high throughput sequencing
Platform:
GPL13112
3 Samples
Download data: TXT
Series
Accession:
GSE43725
ID:
200043725
11.

A Role for WDR5 in Integrating Threonine 11 Phosphorylation to Lysine 4 Methylationon Histone H3 and in Prostate Cancer

(Submitter supplied) Upon androgen stimulation, PKN1-mediated histone H3 threonine 11 phosphorylation (H3T11P) promotes AR target genes activation. However, the underlying mechanism is not completely understood. Here, we show that WDR5, a subunit of the SET1/MLL complex, interacts with H3T11P and this interaction facilitates the recruitment of the SET1/MLL complex and subsequent H3K4 trimethylation (H3K4me3). Using ChIP-seq, we find that androgen stimulation results in a six-fold increase in the number of H3T11P-marked regions and induces WDR5 colocalization to one third of H3T11P-enriched promoters, thus establishing a genome-wide relationship between H3T11P and recruitment of WDR5. more...
Organism:
Homo sapiens
Type:
Genome binding/occupancy profiling by high throughput sequencing
Platform:
GPL11154
6 Samples
Download data: BEDGRAPH, TXT
Series
Accession:
GSE55279
ID:
200055279
12.

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

(Submitter supplied) 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. more...
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing; Other
Platforms:
GPL18573 GPL24676
56 Samples
Download data: TXT
Series
Accession:
GSE206931
ID:
200206931
13.

TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia

(Submitter supplied) The aim of the study was to investigate the role of TGIF1 in MLL-AF9 transformed cells Members of the TALE (Three-amino acid loop extension) family of atypical homeodomain-containing transcription factors are prominent downstream effectors of oncogenic fusion proteins generated from translocations involving the mixed lineage leukemia (MLL) gene. A particular well-characterized member of this protein family is MEIS1, which together with HOXA proteins, orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). more...
Organism:
Mus musculus
Type:
Expression profiling by array
Dataset:
GDS5456
Platform:
GPL6246
6 Samples
Download data: CEL, TXT
Series
Accession:
GSE55713
ID:
200055713
14.

TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemias

(Submitter supplied) Members of the TALE (Three-amino acid loop extension) family of atypical homeodomain-containing transcription factors are prominent downstream effectors of oncogenic fusion proteins generated from translocations involving the mixed lineage leukemia (MLL) gene. A particular well-characterized member of this protein family is MEIS1, which together with HOXA proteins, orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). more...
Organism:
Mus musculus
Type:
Genome binding/occupancy profiling by high throughput sequencing
Platforms:
GPL11002 GPL13112
9 Samples
Download data: BW, TXT
Series
Accession:
GSE55287
ID:
200055287
15.
Full record GDS5456

TGIF1-transduced MLL-AF9-transformed leukemic cells

Analysis of mixed lineage leukemia (MLL)-AF9 transformed cells (MAF9) transduced with TGF-β induced factor 1 (TGIF1). TGIF1 is a member of the TALE (three-amino-acid loop extension) family of homeodomain-containing transcription factors. Results provide insight into the role of TGIF1 in MAF9 cells.
Organism:
Mus musculus
Type:
Expression profiling by array, count, 2 protocol sets
Platform:
GPL6246
Series:
GSE55713
6 Samples
Download data: CEL
DataSet
Accession:
GDS5456
ID:
5456
16.

Genetic deletion or small molecule inhibition of the arginine methyltransferase PRMT5 exhibit anti-tumoral activity in mouse models of MLL-rearranged AML

(Submitter supplied) The hematological malignancies classified as Mixed Lineage leukemias (MLL) harbor fusions of the MLL1 gene to partners that are members of transcriptional elongation complexes. MLL-rearranged leukemias are associated with extremely poor prognosis and response to conventional therapies and efforts to identify molecular targets are urgently needed. Using mouse models of MLL-rearranged acute myeloid leukemia (AML), here we show that genetic inactivation or small molecule inhibition of the protein arginine methyltransferase PRMT5 exhibit anti-tumoral activity in MLL-fusion protein driven transformation. more...
Organism:
Mus musculus
Type:
Expression profiling by high throughput sequencing
Platform:
GPL13112
6 Samples
Download data: TXT
Series
Accession:
GSE100820
ID:
200100820
17.

Synergistic Targeting of FLT3 Mutations in AML via Combined Menin-MLL and FLT3 Inhibition

(Submitter supplied) The interaction of Menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and potential therapeutic opportunity against NPM1 mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias. Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and are particularly common in the NPM1mut subtype. Transcriptional profiling upon pharmacological inhibition of the Menin-MLL complex revealed specific changes in gene expression with downregulation of the MEIS1 transcription factor and its transcriptional target gene FLT3 being most pronounced. more...
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing
Platform:
GPL20301
24 Samples
Download data: TXT
18.

Zinc finger protein 521 overexpression is a feature of MLL-rearranged acute myeloid leukemia and contributes to the maintenance of myeloid differentiation block

(Submitter supplied) ZNF521 is a multiple zinc finger transcription factor previously identified because abundantly and selectively expressed in normal CD34+ hematopoietic stem and progenitor cells. From microarray datasets, aberrant expression of ZNF521 has been reported in both pediatric and adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. However, a proper validation of microarray data is lacking, likewise ZNF521 contribution in MLL-rearranged AML is still uncertain. more...
Organism:
Homo sapiens
Type:
Expression profiling by array
Platform:
GPL570
6 Samples
Download data: CEL
Series
Accession:
GSE79110
ID:
200079110
19.

Genome-wide analysis of gene expression in MLL translocation transformed mouse leukemia cell lines

(Submitter supplied) The purpose of this study is to investigate the transcriptional programs as it relates to disease latency initiated by different MLL fusion proteins, including: MLL-AF1p, MLL-AF6, MLL-Gas7, MLL-AF9 and MLL-ENL. Leukemia cell lines were established by transforming kit+ mouse bone marrow cells with retroviruses coding MLL-AF1p, MLL-AF6, MLL-Gas7, MLL-AF9 or MLL-ENL. At early phase after the cell lines were established, cells growing at exponential phase (cell density at 0.5~1x106/ml) were harvested for RNA extraction and sequencing purpose.
Organism:
Mus musculus
Type:
Expression profiling by high throughput sequencing
Platform:
GPL13112
12 Samples
Download data: TXT
Series
Accession:
GSE73457
ID:
200073457
20.

Affymetrix Human Exon 1.0 ST array assay of 15 human MLL-associated samples and 9 human normal bone marrow [HuEx-1_0-st]

(Submitter supplied) To identify potential target genes of leukemia-related miRNAs such as miR-196b and miR-150 in human MLL-associated leukemia, we performed Affymetrix Human Exon 1.0 ST array assay of 15 human MLL-associated samples and 9 human normal bone marrow (including 3 each of CD34+, CD33+, and MNC) cell samples.
Organism:
Homo sapiens
Type:
Expression profiling by array
Platform:
GPL5175
24 Samples
Download data: CEL
Series
Accession:
GSE34184
ID:
200034184
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