Ontology highlight
ABSTRACT:
PROVIDER: PRJNA759750 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15711800_1.fastq.gz | Fastqsanger.gz | |||
| SRR15711800_2.fastq.gz | Fastqsanger.gz | |||
| SRR15711801_1.fastq.gz | Fastqsanger.gz | |||
| SRR15711801_2.fastq.gz | Fastqsanger.gz | |||
| SRR15711802_1.fastq.gz | Fastqsanger.gz |
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Project description:Myelofibrosis is often associated with the myeloproliferative neoplasms and expression of oncogenic JAK2 mutants. Patients with myelofibrosis have diminished quality of life due to systemic symptoms arising from fibrotic changes in the bone marrow. The introduction of the JAK2 inhibitor, ruxolitinib, has been of benefit in the treatment of myelofibrosis patients however, it is not curative and there is still a requirement for new targeted therapies to eradicate the cells at the heart of myelofibrosis pathology. Repurposing drugs bypasses many of the hurdles present in drug development, such as toxicity and pharmacodynamic profiling. To this end we undertook a re-analysis of our pre-existing proteomic data sets to identify perturbed biochemical pathways and their associated drugs/inhibitors to potentially target the cells driving myelofibrosis. This approach identified CBL0137 as a candidate for targeting JAK2 mutant driven malignancies. We therefore assessed CBL0137 as a new agent to extinguish JAK2 mutant primitive cells and show its ability to preferentially target cells from MF patients compared to healthy control cells. Further we define its mechanistic action in primary haemopoietic progenitor cells and demonstrate its ability to reduce splenomegaly and reticulocyte number in a transgenic murine model of myeloproliferative neoplasms.
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Project description:Characterization of ~68 cell lines derived from human sarcoma and 5 normal counterpart cells, including drug sensitivity testing, gene expression profiling and microRNA expression profiling have been completed. Data and tools for searching these data will be made publicly available through the NCI Developmental Therapeutics Program. The raw data (RCC files) are provided through the GEO website. Sarcoma represents a variety of cancers at arise from cells of mesenchymal origin and have seen limited treatment advances in the last decade. Drug sensitivity data coupled with the transcription and microRNA profiles of a cohort of sarcoma cell lines may help define novel treatment paradigms. For each cell line, microRNA expression was measured on nCounter miRNA Expression Arrays (Nanostring Technologies), providing multiplexed, digital detection and counting of 800 human microRNA's. Please note that there are 2 replicates included in the study: A-204-rep1 and A-204-rep2, ES-4-rep1 and ES-4-rep2 resulting total 77 samples.
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