Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA302301 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The Baf3 are dependent on IL-3 for grwoth however transformation by BCR -ABL oncogene causes BAf3 cells independent of IL-3. The BAf3 cells expressing BCR-ABL are dependent on continuous expression of BCR_ABL for growth. Inhibitionof BCR-ABL by its inhibitor Imatinib cause these cells to undergo apoptosis. When these cells are grown with IL-3 these cells do not respond to Imatinib mediated grwoth arrest.
2017-03-20 | GSE75057 | GEO
Project description:BAF3 cells harboring constitutively expressing BCR-ABL were grown with or without IL-3 supplement and treated with Imatinib and live cells from the IL-3 and without IL-3 were sorted by FACS.
2017-03-20 | GSE75056 | GEO
Project description:Purpose: BCR-ABL-positive acute lymphoid leukemia (ALL) has a dire prognosis. Despite improved disease-free survival due to implementation of TKIs in front-line therapy, patient survival remains unsatisfactory and there exists a need for new treatments. Therefore, we performed a drug screen based on competition between untransformed cells and BCR-Abl-transformed cells, and identified several compounds that selectively reduce the competitive fitness of BCR-Abl-transformed cells. Using a systems approach we discovered that one of these compounds, DJ34, induces potent activation of p53 and rapid degradation of c-Myc, which is frequently deregulated in leukemia. DJ34 treatment induced apoptosis, cell cycle arrest and cell differentiation and inhibited survival of primary AML cells, both ex vivo and in a zebrafish PDX model. The goals of this study is to check the effect of DJ34 on transcriptome profile of BCR-Abl expressing BaF3 cells. Methods: mRNA profiles of BaF3 cells expressing BCR-Abl treated with DMSO or 20µM DJ34 for 6hrs were generated by Illumina Hiseq 4000 SE50, in triplicate. Then, clean reads (as provided by BGI) were mapped to the GRCm38.85 genome assembly using Tophat2 (v. 2.1.1) [1] using default options BAM files were indexed using SAMtools [2]. Differential expression data was produced using cuffquant and cuffdiff with default options, from the cufflinks suite (v 2.2.1 / SVN rev 4237) [3]. Reference genome for the primary assembly and gene annotations used are revision 85 of GRCm38, from ensembl.org. The .Bam and .tdf files were used for quantification and visualization in IGV respectively. [1] Kim, Daehwan, et al. "TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions." Genome biology 14.4 (2013): R36. [2] Li, Heng, et al. "The sequence alignment/map format and SAMtools." Bioinformatics 25.16 (2009): 2078-2079. [3] Trapnell, Cole, et al. "Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks." Nature protocols 7.3 (2012): 562. Results: Using data analysis workflow described above, we identified differentially expressed genes in the control and DJ34 treated BaF3 cells expressing BCR-Abl cells. Conclusions: Competition based drug screening has identified DJ34 that selectively erradicates BCR-Abl expressing BaF3 cells. Our RNa-seq basaed transcriptome analysis shows that DJ34 induces potent activation of p53 and rapid degradation of c-Myc, which is frequently deregulated in leukemia.
2020-12-07 | GSE100678 | GEO
Project description:Interferon is effective at inducing complete remissions in patients with Chronic Myelogenous Leukemia (CML), and evidence supports an immune mechanism. Here we show that the Type I Interferons (alpha and beta) regulate expression of the Interferon consensus sequence binding protein (ICSBP) in bcr-abl transformed cells and as shown previously for ICSBP, induce a vaccine-like immunoprotective effect in a murine model of bcr-abl induced leukemia. We identify the chemokines CCL6 and CCL9 as genes prominently induced by the Type I Interferons and ICSBP, and demonstrate that these immunomodulators are required for the immunoprotective effect of ICSBP expression. Insights into the role of these chemokines in the anti-leukemic response of interferons suggest new strategies for immunotherapy of CML. Experiment Overall Design: Total RNA was isolated from parental BaF3 cells as well as BaF3 cells expressing BCR-ABL, ICSBP, or both BCR-ABL and ICSBP. Using standard Affymetrix protocols the RNA samples were analyzed for gene expression using Affymetrix mouse 430_2 whole genome microarrays arrays. A threshold value of 50 was set for all genes and the list of genes filtered to include only those that had at least one Present flag ("P" flag) in one of the 4 conditions. For each gene, the ratio of its expression in a particular condition and its expression in parental BaF3 cells was determined. Only genes that had at least a 3-fold up or down change in expression were considered, leaving a set of 1431 genes for further analysis. K-means clustering with Gene cluster 3.0 was used to group these 1431 genes into 15 clusters and JavaTree was used to visualize the results.
2009-01-25 | E-GEOD-14416 | biostudies-arrayexpress
Project description:We previously demonstrated that Alox5 deficiency impairs the function of LSCs and prevents the initiation of BCR-ABL-induced CML. To identify the pathways in which Alox5 gene regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Alox5-/- LSCs. The result was validated by quantitative real-time PCR analysis of non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Alox5-/- LSCs. We have shown that Alox5 is a critical regulator of leukemia stem cells (LSCs) in a BCR-ABL-induced chronic myeloid leukemia (CML) mouse model, and we hypothesize that the Alox5 pathway represents a major molecular network that regulates LSC function. Therefore, we sought to further dissect this pathway by comparing the gene expression profiles of wild type and Alox5-/- LSCs derived from our mouse model for BCR-ABL-induced CML. DNA microarray analysis revealed a small group of candidate genes that exhibited changes in the levels of transcription in the absence of Alox5 expression. In particular, we noted that the expression of the Msr1 gene was up-regulated in Alox5-/- LSCs, suggesting that Msr1 might suppress the proliferation of LSCs. Using our CML mouse model, we show that Msr1 is down-regulated by BCR-ABL and this down-regulation is partially restored by Alox5 deletion, and that Msr1 deletion causes acceleration of CML development. Moreover, Msr1 deletion markedly increases LSC function through its effects on cell cycle progression and apoptosis. We also show that Msr1 affects CML development by regulating the PI3K-AKT pathway and ?-Catenin. Together, these results demonstrate that Msr1 suppresses LSCs and CML development. The enhancement of Msr1 function may be of significance in the development of novel therapeutic strategies targeting CML. To identify genes that are regulated by BCR-ABL in LSCs and LSCs without Alox5 gene, we compared the gene profile between wild type(WT) LSCs or Alox5-/- LSCs.
2011-05-17 | E-GEOD-29347 | biostudies-arrayexpress
Project description:Oncogenic tyrosine kinases, such as BCR-ABL, TEL-ABL, TEL-PDGF-beta-R and FLT3-ITD, play a major role in the development of hematopoietic malignancy. They activate many of the same signal transduction pathways. To identify the critical target genes required for transformation in hematopoietic cells, we used a comparative gene expression strategy in which selective small molecules were applied to 32Dcl3 cells that had been transformed to factor-independent growth by these respective oncogenic alleles. Experiment Overall Design: In our microarray study, we have total 22 samples from four different cell lines expressing BCR-ABL, TEL-ABL, FLT3-ITD or TEL-PDGF-betaR. Each cell line was treated with specific small molecule inhibitors for 4 hours, then RNA was extracted and cRNA was hybridized to Affymetrix U74 oligonucleotide arrays. Untreated cells or cells treated with unrelated inhibitors were used as controls or references. We have three replicates and six references obtained from three independent experiments for cells expressing BCR-ABL or FLT3-ITD. We have one treated and one untreated sample for each cell line expressing TEL-ABL or TEL-PDGF-beta-R.
2008-10-21 | E-GEOD-11794 | biostudies-arrayexpress
Project description:We previously demonstrated that Alox5 deficiency impairs the function of LSCs and prevents the initiation of BCR-ABL-induced CML. To identify the pathways in which Alox5 gene regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Alox5-/- LSCs. The result was validated by quantitative real-time PCR analysis of non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Alox5-/- LSCs. We have shown that Alox5 is a critical regulator of leukemia stem cells (LSCs) in a BCR-ABL-induced chronic myeloid leukemia (CML) mouse model, and we hypothesize that the Alox5 pathway represents a major molecular network that regulates LSC function. Therefore, we sought to further dissect this pathway by comparing the gene expression profiles of wild type and Alox5-/- LSCs derived from our mouse model for BCR-ABL-induced CML. DNA microarray analysis revealed a small group of candidate genes that exhibited changes in the levels of transcription in the absence of Alox5 expression. In particular, we noted that the expression of the Msr1 gene was up-regulated in Alox5-/- LSCs, suggesting that Msr1 might suppress the proliferation of LSCs. Using our CML mouse model, we show that Msr1 is down-regulated by BCR-ABL and this down-regulation is partially restored by Alox5 deletion, and that Msr1 deletion causes acceleration of CML development. Moreover, Msr1 deletion markedly increases LSC function through its effects on cell cycle progression and apoptosis. We also show that Msr1 affects CML development by regulating the PI3K-AKT pathway and β-Catenin. Together, these results demonstrate that Msr1 suppresses LSCs and CML development. The enhancement of Msr1 function may be of significance in the development of novel therapeutic strategies targeting CML.
2011-05-17 | GSE29347 | GEO
Project description:Expression profile of Imatinib treated BAF3 -BCR-ABL cells
| PRJNA302300 | ENA
Project description:K562 cells were treated with the BCR-ABL kinase inhibitor dasatinib over an extended period of time to determine how BCR-ABL inhibition affects BCR-ABL-dependent negative feedback and erythropoietin receptor (EPO-R) signaling. Specifically, what types of changes (upregulation versus downregulation) occur in both the negative and positive regulators of growth-factor receptor signaling.
2013-09-24 | GSE51083 | GEO
Project description:MiR-142 is dynamically expressed and plays a regulatory role in hematopoiesis. Based on the simple observation that miR-142 levels are significantly lower in CD34+CD38- cells from blast crisis (BC) chronic myeloid leukemia (CML). CML patients compared with chronic phase (CP) CML patients (p=0.002), we hypothesized that miR-142 deficit plays a role in BC transformation. To test this hypothesis, we generated a miR-142 KO BCR-ABL (i.e., miR-142−/−BCR-ABL) mouse by crossing a miR-142−/− mouse with a miR-142+/+BCR-ABL mouse. While the miR-142+/+BCR-ABL mice developed and died of CP CML, the miR-142−/−BCR-ABL mice developed a BC-like phenotype in the absence of any other acquired gene mutations and died significantly sooner than miR-142+/+BCR-ABL CP controls (p=0.001). Leukemic stem cell (LSC)-enriched Lineage-Sca-1+c-Kit+ cells (LSKs) from diseased miR-142−/−BCR-ABL mice transplanted into congenic recipients, recapitulated the BC features thereby suggesting stable transformation of CP-LSCs into BC-LSCs in the miR-142 KO CML mouse. Single cell (sc) RNA-seq profiling showed that miR-142 deficit changed the cellular landscape of the miR-142−/−BCR-ABL LSKs compared with miR-142+/+BCR-ABL LSKs with expansion of myeloid-primed and loss of lymphoid-primed factions. Bulk RNA-seq analyses along with unbiased metabolomic profiling and functional metabolic assays demonstrated enhanced fatty acid β-oxidation (FAO) and oxidative phosphorylation (OxPhos) in miR-142−/−BCR-ABL LSKs vs miR-142+/+BCR-ABL LSKs. MiR-142 deficit enhanced FAO in miR-142−/−BCR-ABL LSKs by increasing the expression of CPT1A and CPT1B, that controls the cytosol-to-mitochondrial acyl-carnitine transport, a critical step in FAO. MiR-142 deficit also enhanced OxPhos in miR-142−/−BCR-ABL LSKs by increasing mitochondrial fusion and activity. As the homeostasis and activity of LSCs depend on higher levels of these oxidative metabolism processes, we then postulate that miR-142 deficit is a potentially druggable target for BC-LSCs. To this end, we developed a novel CpG-miR-142 mimic oligonucleotide (ODN; i.e., CpG-M-miR-142) that corrected the miR-142 deficit and alone or in combination with a tyrosine kinase inhibitor (TKI) significantly reduced LSC burden and prolonged survival of miR-142−/−BCR-ABL mice. The results from murine models were validated in BC CD34+CD38- primary blasts and patient-derived xenografts (PDXs). In conclusion, an acquired miR-142 deficit sufficed in transforming CP-LSCs into BC-LSCs, via enhancement of bioenergetic oxidative metabolism in absence of any additional gene mutations, and likely represent a novel therapeutic target in BC CML.
2023-01-13 | ST002446 | MetabolomicsWorkbench