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SRP055108
Homo sapiens
6 Downloadable Samples
IlluminaHiSeq2000
Description
We identify perhexiline, a small molecule inhibitor of mitochondrial carnitine palmitoyltransferase-1, as a HES1-signature antagonist drug with robust antileukemic activity against NOTCH1 induced leukemias in vitro and in vivo. Overall design: RNA-Seq from CUTLL1 cell lines treated with Perhexiline or vehicle for 3 days
Publication Title
Therapeutic targeting of HES1 transcriptional programs in T-ALL.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 52 Downloadable Samples
- Illumina HiSeq 2500
Description
NOTCH1 is mutationally activated in ~15% of cases of chronic lymphocytic leukaemia (CLL), but its role in B-cell development and leukemogenesis is not known. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ~50% of peripheral blood CLL cases lacking gene mutations. We identify a ‘NOTCH1 CLL gene expression signature’ in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival and signal transduction physiology. In particular, we show that MYC is a direct target of NOTCH1 via B-cell specific distal regulatory elements, thus implicating this oncogene in the pathogenesis of the disease. Overall design: RNA-Seq analysis
Publication Title
Common nonmutational <i>NOTCH1</i> activation in chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina HiSeq 2000
Description
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive lymphoid tumor derived from malignant transformation of T follicular helper (Tfh) cells. Genetically, AITL is characterized by loss of function mutations in the Ten-Eleven Translocation 2 (TET2) epigenetic tumor suppressor and a highly recurrent mutation (p.Gly17Val, G17V) in the RHOA small GTPase gene Moreover, RHOA G17V expression in Tet2 deficient hematopoietic progenitors resulted in the specific development of lymphoid tumors resembling human AITL. Notably, inhibition of ICOS signaling impaired the growth of RHOA G17V-induced mouse lymphomas in vivo, thus providing a potential new rational approach for the treatment of AITL. Overall design: We analyzed mRNA expression profiles of primary tumor cells expressing Rhoa G17V or Rhoa wild type.
Publication Title
RHOA G17V Induces T Follicular Helper Cell Specification and Promotes Lymphomagenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To investigate the underlying mechanisms mediating resistance to NOTCH inhibition in Pten-null T-ALL tumor cells we performed gene expression profiling of isogenic Pten-positive and Pten-deleted leukemia lymphoblasts after acute treatment with DBZ in vivo.
Publication Title
Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We sought to determine genes whose expression changed upon treatment with a selective inhibitor of class I PI3 kinase.
Publication Title
Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Unsupervised hierarchical clustering revealed a strong similarity in gene modulation resulting from either compound treatment or BRAF ablation mediated by RNA interference relative to DMSO-treated control samples .
Publication Title
Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Basal gene expression levels were determined by global gene expression profiling of breast cancer cell lines.
Publication Title
In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to profile 30 human primary breast tumors and determine global gene expression patterns and molecular subtypes
Publication Title
In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models.
Sample Metadata Fields
No sample metadata fields
View Samples