Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA302300 | ENA |
REPOSITORIES: ENA
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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:In our previous study, the roles of heterogeneous nuclear ribonucleoprotein D-like (HNRPDL) in CML cells were revealed. We found that overexpression of HNRPDL transformed murine BaF3 cells and induced lethal mice leukemia. Conversely, HNRPDL silencing inhibited colony-forming cell (CFC) production of CML CD34+ cells and attenuated BCR-ABL induced mice leukemia. In addition, HNRPDL modulated imatinib response of K562 cells and HNRPDL silencing sensitized CML CD34+ cells to imatinib treatment. To obtain molecular insights of how HNRPDL modulates the growth and imatinib response of human CML cells, we generated microarray data comparing HNRPDL silenced K562 cells with control (Scramble) cells.
2019-06-20 | GSE132975 | 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:K562 cells untreated (S) and treated (S+IM) with Imatinib as well as sensitive (S+IM) and resistant (R) to imatinib were subjected to labelled quantification by iTRAQ to identify Bcr-Abl downstream signaling components and proteins modulated in resistance respectively
2021-10-05 | PXD025173 | Pride
Project description:Gene expression profile variation between 4 BCR-Abl transduced cell lines: <br> 1-Mouse DA1-3b cell line as reference, <br> 2-DR1 imatinib resistant clone with E255K BCR-abl mutation<br> 3-DRBMSR 2 dasatinib resistant clone with E255K and T315I BCR-Abl mutation.<br> 4-DRBMSR 7 dasatinib resistant clone with E255K and T315I and V299L BCR-Abl mutation<br> <br> BCR-ABL is an oncogenic tyrosine kinase involved in the development of chronic myelogenous leukaemia (CML).
2007-08-01 | E-MEXP-772 | biostudies-arrayexpress
Project description:Background: Chronic myeloid leukemia (CML) is a malignant clonal disorder of the hematopoietic system caused by the expression of the BCR/ABL fusion oncogene. It is well known that CML cells are genetically unstable. However, the mechanisms by which these cells acquire genetic alterations are poorly understood. Imatinib mesylate (IM) is the standard therapy for newly diagnosed CML patients. IM targets the oncogenic kinase activity of BCR-ABL. Objective: To study the gene expression profile of BM hematopoietic cells in the same patients with CML before and one month after imatinib therapy. Methods: Samples from patients with CML were analyzed using Affymetrix GeneChip Expression Arrays. Results: A total of 594 differentially expressed genes, most of which (393 genes) were downregulated, as a result of imatinib therapy were observed. Conclusions: The blockade of oncoprotein Bcr-abl by imatinib could cause a decrease in the expression of key DNA repair genes, and cells try to restore the normal gene expression levels required for cell proliferation and chromosomal integrity.
2014-01-01 | GSE33075 | GEO
Project description:One of the main objective of this study is to characterize Imatinib induced MSCs-mediated resistance evolution in BCR-ABL+ ALL. Tyrosine kinase inhibitor (TKI) Imatinib (IM) is used as a frontline therapy for BCR-ABL–positive (BCR-ABL+) acute lymphoblastic leukemia (ALL). However, resistance to IM therapy develops rapidly in a substantial proportion of treated patients, and the molecular mechanisms underlying the resistance are poorly understood. In this study, we identified a novel cascade of consequential events that are initiated by IM, which traverse through mesenchymal stem/stromal cells (MSCs) to leukemic cells, and lead to IM resistance. Our data showed that MSCs exposed to IM were decreased in their stemness and acquired a new functional status that enabled the formation of leukemic cell niches. These MSCs had increased expression of genes encoding chemo-attractants, adhesion molecules, and pro-survival stimulant growth factors. We found that BCR-ABL+ leukemic cells persistently exposed to IM were able to switch from BCR-ABL–driven signaling to growth factor–driven signaling for survival, and this switch was reversible. Blocking both the BCR-ABL–driven pathway and the growth factor–driven JAK pathway effectively eradicated the leukemic cell niches. Our findings illustrate TKI-induced, MSC-mediated drug resistance, suggesting an effective way to eliminate this type of drug resistance in patients with BCR-ABL+ ALL. Gene expression signatures were compared from triplicate samples of MSCs that were either treated with vehicle or imatinib for 32, 64 and 96 hours.
2015-09-01 | E-GEOD-56472 | biostudies-arrayexpress
Project description:Aberrantly expressed long noncoding RNAs (lncRNAs) have been described in diverse human diseases and cancer development. Chronic myeloid leukemia (CML) is a hematological malignancy induced by Bcr-Abl hybrid gene. Owing to the development of tyrosine kinase inhibitors (TKIs), especially the first-generation Imatinib, over 90% of CML patients can be cured in recent years. Here we attempt to identify Imatinib-inducible lncRNAs associated with CML by analyzing lncRNA expression profiles in K562 cells after Imatinib or control treatment. LncRNA microarray analysis revealed that numerous lncRNAs were differentially expressed in K562 cells after Imatinib treatment. In this study, we focus on a conserved, Imatinib-inducible lncRNA (IIR) family, named lncRNA-IIRX. Upregulation of lncRNA-IIRX has been detected in both human and mouse Abl-transformed cell lines after Imatinib treatment. Interestingly, lncRNA-IIRX levels were significantly lower in leukemic cells derived from Bcr-Abl-positive ALL patients than those in normal control group. Furthermore, altering lncRNA-IIRX expression remarkably affected survival of Abl-transformed leukemic cells, and tumorigensis induced by these leukemic cells in xenograft mouse model. Knockdown of lncRNA-IIRX in transgenic mice significantly promoted Bcr-Abl-mediated primary bone marrow transformation, and leukemia development in leukemia mouse model. These results indicate that lncRNA-IIRX functions as a suppressor gene in Bcr-Abl-induced tumorigenesis, and may provide novel insights into complicated mechanisms underlying cellular transformation by Bcr-Abl oncogene. This microarray was performed to identify Imatinib-inducible lncRNAs associated with CML.
2019-04-17 | GSE119770 | GEO
Project description:Gene expression profile of Baf3 cells conditionally expressing BCR-ABL in presence and absence of Growth factor IL-3
| PRJNA302301 | ENA