GEO DataSets

(Submitter supplied) Children with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) have a poor prognosis with few therapeutic options. Multiple lines of evidence point towards the enzyme dihydroorotate dehydrogenase (DHODH) as a metabolic vulnerability in dysregulated and malignant T‑cells. DHODH catalyzes the fourth step of de novo pyrimidine nucleotide synthesis (e.g., uridine, cytidine). Therefore, inhibiting DHODH via small molecule inhibitors (DHODHi) rapidly leads to the depletion of intracellular pyrimidine pools and forces cells to rely on extracellular salvage. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

12 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing; Other

Platform:

GPL19057

43 Samples

Download data

(Submitter supplied) Investigating genes that increase or decrease treatment efficacy of AG636 in MLL-AF9; KrasG12D (MN) AML cells.

Organism:

Mus musculus

Type:

Other

Platform:

GPL19057

7 Samples

Download data: TXT

(Submitter supplied) Investigation of the transcriptional profile of AML in response to DHODH inhibition by AG636. RUNX1-RUNX1T1 cells were transplanted into Ptprca recipients. Mice bearing tumors were treated with AG636 for one day. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated and RNA sequencing performed.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

8 Samples

Download data: TXT

(Submitter supplied) Investigation of the transcriptional profile of AML in response to DHODH inhibition by AG636. I1DN model was generated by co-transduction of foetal liver derived HSPCs with constructs encoding IDH1R132H, DNMT3AR882H and NrasG12D. Cells were transplanted into Ptprca recipients. Mice bearing I1DN tumors were treated with AG636 for one day. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated and RNA sequencing performed.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

6 Samples

Download data: TXT

(Submitter supplied) Investigation of the transcriptional profile and compared with the genome accessibility (using ATAC-seq) in MN cells. Mice bearing MN tumors were treated with AG636 for 2 days. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated. RNA sequencing and ATAC-seq were performed.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

4 Samples

Download data: TXT

(Submitter supplied) Investigation of the transcriptional profile of MLL-rearranged AML in response to DHODH inhibition by AG636. Chemo-refractory syngeneic murine AML model driven by doxycycline-inducible expression of MLL-AF9 and constitutive expression of oncogenic Nras (MN) was transplanted into Ptprca recipients. Mice bearing MN tumors were treated with doxycycline or AG636 for one or four days. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated and RNA sequencing performed.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

14 Samples

Download data: TXT

(Submitter supplied) Investigation of the chromatin accessibility in MN cells. Mice bearing MN tumors were treated with AG636 for 2 days. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated. RNA sequencing and ATAC-seq were performed.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

4 Samples

Download data: BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL19057 GPL18573

34 Samples

Download data: BW

(Submitter supplied) Despite intensive therapy, children with high-risk neuroblastoma are at risk of treatment failure. We applied a multi-omic system approach to evaluate metabolic vulnerabilities in human neuroblastoma. We combined metabolomics, CRISPR screening and transcriptomic data across >700 solid tumor cell lines and identified dihydroorotate dehydrogenase (DHODH), a critical enzyme in pyrimidine synthesis, as a potential treatment target. more...

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL18573 GPL19057

27 Samples

Download data: CSV

(Submitter supplied) Despite intensive therapy, children with high-risk neuroblastoma are at risk of treatment failure. We applied a multi-omic system approach to evaluate metabolic vulnerabilities in human neuroblastoma. We combined metabolomics, CRISPR screening and transcriptomic data across >700 solid tumor cell lines and identified dihydroorotate dehydrogenase (DHODH), a critical enzyme in pyrimidine synthesis, as a potential treatment target. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

7 Samples

Download data: BW

(Submitter supplied) PTC299 was identified as an inhibitor of VEGFA mRNA translation in a phenotypic screen and evaluated in the clinic for treatment of solid tumors. To guide precision cancer treatment, we performed extensive biological characterization of the activity of PTC299 and demonstrated that inhibition of VEGF production and cell proliferation by PTC299 is linked to a decrease in uridine nucleotides by targeting dihydroorotate dehydrogenase (DHODH), a rate limiting enzyme for de novo pyrimidine nucleotide synthesis. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

8 Samples

Download data: CEL

(Submitter supplied) Agents targeting metabolic pathways form the backbone of standard oncology treatments, though a better understanding of differential metabolic dependencies could instruct more rationale-based therapeutic approaches. We performed a chemical biology screen that revealed a strong enrichment in sensitivity to a novel dihydroorotate dehydrogenase (DHODH) inhibitor, AG-636, in cancer cell lines of hematologic versus solid tumor origin. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL23227

24 Samples

Download data: TXT

(Submitter supplied) We have previously observed protein level changes after treating human cells with two novel inhibitors of the enzyme DHODH. This study was designed to study up to what degree these protein differences can be also observed at level of mRNA. As part of the de novo pyrimidine synthesis pathway, DHODH inhibition is expected to decrease the levels of total RNA in cells. However, some effector proteins associated with the p53 pathway are increased after treatment with these inhibitors. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

9 Samples

Download data: TXT

(Submitter supplied) We aim to gain insight into the changes of gene expression induced by ASLAN003, a novel, potent Dihydroorotate Dehydrogenase (DHODH) Inhibitor

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

12 Samples

Download data: TXT

(Submitter supplied) Cells were cultured for a period of six months in slowly escalating concentrations of two small molecules (Compound 3 and Compund 7) whose protein target was unknown. Over this six month period, the cells cultured in C03 and C07 became resistant to the differentiation and growth inhibitory effects of the the compounds. Total RNA was harvested for RNA-sequencing.

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL13112 GPL11154

6 Samples

Download data: TXT

(Submitter supplied) Lysozyme-GFP ER-HoxA9 cells were cultured in the presence of estradiol (active ER-HoxA9) or in the absence of estradiol (inactive ER-HoxA9). Samples were taken at 10 time points over a 120 hour time course of myeloid differentiation to examine those gene expression changes that accompany differentiation upon the release of HoxA9 differentiation arrest.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

24 Samples

Download data: TXT

(Submitter supplied) Mice bearing an MLL/AF9 leukemia were treated with vehicle or brequinar every three days for a total of four doses. Mice were euthanized for collection of the bone marrow cells. The leukemia cells were purified by FACS (fluorescence activated cell sorting) and total RNA was prepared from the purified leukemia cells.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

2 Samples

Download data: TXT

(Submitter supplied) We performed in-vivo selection of human patient derived colorectal cancer xenografts. 4 independent highly-liver metastatic sub-lines (lvm PDXs) were generated. Those lvm PDXs were harvested with the corresponding parental PDX tumors from mice and then we performed MACS mice cell depletion followed by FACS sorting to obtain human EpCAM positive and mice MHC negatitve populations. total RNA was extracted from those ex-vivo tumors and high-throuput sequencing was performed

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

8 Samples

Download data: FPKM_TRACKING, XLSX

(Submitter supplied) The development of different generations of BCR-ABL1 tyrosine kinases inhibitors (TKIs) has led the overall survival (OS) of the chronic myeloid leukemia (CML) patients to become almost similar to that of a control population without leukemia, but the TKI therapy can be successfully discontinued only in half of those who are achieving a deep molecular response, that eans in approximately 15-20% of the entire population. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

10 Samples

Download data: TXT