Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA253778 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:mRNA expression data from BCR-ABL, MYC and CD22DE12 transgenic mouse models
| PRJNA253779 | ENA
Project description:Leukemic splenocytes from these commercial transgenic mice that developed fatal leukemia with massive splenomegaly were isolated at the time of the necropsy and subjected to gene expression profiling and phosphoprotein profiling in side by side comparison with CD22DE12-Tg BPL or CD22DE12_BCR-ABL double transgenic cells. Mouse leukemia cells were isolated from markedly enlarged spleens of CD22DE12-Tg (N=2), BCR-ABL-Tg (N=2), Eµ-MYC Tg mice (N=2) and Splenocytes from wildtype healthy C57BL/6 mice served as controls (N=4).
2015-06-25 | E-GEOD-58872 | biostudies-arrayexpress
Project description:Gene expression profiling in BCR/ABL expressing LSCs and BCR/ABL expressing Alox5-/-LSCs
| PRJNA138603 | ENA
Project description:Gene expression profiling in BCR/ABL-expressing LSCs and BCR/ABL-expressing Hif1a-/-LSCs
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Project description:Gene expression profiling in BCR-ABL expressing LSCs and BCR-ABL-BLK expressing LSCs
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Project description:BCR-Abl is a driver oncogene that causes chronic myeloid leukemia and a subset of acute lymphoid leukemias. Although tyrosine kinase inhibitors provide an effective treatment for these diseases, they generally do not kill leukemic stem cells. Leukemic stem cells are cancer-initiating cells that compete with normal hematopoietic stem cells for the bone marrow niche. Using BCR-Abl as a model oncogene, we performed a drug screen based on competition between isogenic untransformed cells and BCR-Abl-transformed cells, and identified several compounds that selectively target BCR-Abl-transformed cells. Systems-level analysis of one of these novel compounds, DJ34, revealed that it induced depletion of c-Myc and activation of p53. c-Myc depletion occurred in a wide range of tumor types, including leukemia, lymphoma, lung, glioblastoma and breast cancer. Further analyses revealed that DJ34 interferes with c-Myc synthesis at the level of transcription, and we provide data showing that DJ34 is a DNA intercalator and topoisomerase II inhibitor. Physiologically, DJ34 induced apoptosis, cell cycle arrest and cell differentiation, and primary leukemic stem cells were particularly sensitive to DJ34. Taken together, we have identified a novel compound that dually targets c-Myc and p53 in a wide variety of cancers, and with particularly strong activity against leukemic stem cells.
2020-12-07 | PXD018812 | Pride
Project description:Background In the ongoing battle against BCR-ABL+ leukemia, despite significant advances with tyrosine kinase inhibitors (TKIs), the persistent challenges of drug resistance and the enduring presence of leukemic stem cells (LSCs) remain formidable barriers to achieving a cure. Methods In this study, we demonstrated that Disulfiram (DSF) induces ferroptosis to synergize with TKIs in inhibiting BCR-ABL+ cells, particularly targeting resistant cells and LSCs, using cell models, mouse models, and primary cells from patients. We elucidated the mechanism by which DSF promotes GPX4 degradation to induce ferroptosis through immunofluorescence, co-immunoprecipitation (CO-IP), RNA sequencing, lipid peroxidation assays, and rescue experiments. Results Here, we present compelling evidence elucidating the sensitivity of DSF, an FDA-approved drug for alcohol dependence, towards BCR-ABL+ cells. Our findings underscore DSF's ability to selectively induce a potent cytotoxic effect on BCR-ABL+ cell lines and effectively inhibit primary BCR-ABL+ leukemia cells. Crucially, the combined treatment of DSF with TKIs selectively eradicates TKI-insensitive stem cells and resistant cells. Of particular note is DSF's capacity to disrupt GPX4 stability, elevate the labile iron pool, and intensify lipid peroxidation, ultimately leading to ferroptotic cell death. Our investigation shows that BCR-ABL expression induces alterations in cellular iron metabolism and increases GPX4 expression. Additionally, we demonstrate the indispensability of GPX4 for LSC development and the initiation/maintenance of BCR-ABL+ leukemia. Mechanical analysis further elucidates DSF's ability to circumvent resistance by reducing GPX4 levels through the disruption of its binding with HSPA8, thereby promoting GPX4 ubiquitination and subsequent degradation. Furthermore, the combined treatment of DSF with TKIs effectively targets both BCR-ABL+ blast cells and drug-insensitive LSCs, conferring a significant survival advantage in mouse models. Conclusion In summary, the dual inhibition of GPX4 and BCR-ABL presents a promising therapeutic strategy to synergistically target blast cells and drug-insensitive LSCs in patients, offering potential avenues for advancing leukemia treatment.
2024-09-05 | GSE276122 | GEO
Project description:We apply cellular reprogramming to an induced pluripotent cell state to human cell lines and primary samples exhibiting Chronic Myoloid Leukemia (CML). Addtionally, we generated an inducible CML BCR-ABL transgenic mouse model. Biological replicates (duplicates) were available for all samples. DNA methylation profiles for all cells were generated using Reduced Representation Bisulfite Sequencing (RRBS). DNA methylation profiling of human leukemia cell lines, primary cells, derived iPS cells as well as transgenic mouse models for CML in duplicates using RRBS.
2015-07-14 | E-GEOD-50456 | biostudies-arrayexpress