Genomic expression analysis of K562 cells expressing shRNA targeting lncRNA-IIRX and control cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE120337 | GEO | 2019/04/17
REPOSITORIES: GEO
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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:Aberrant long noncoding RNA (lncRNA) expression has been described in many human malignancies, including leukemia. Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) is a stem cell disease induced by Bcr-Abl hybrid gene. Here we attempt to identify lncRNAs associated with CML by analyzing lncRNA expression profiles in K562 cells when Bcr-Abl gene silenced. LncRNA microarray analysis revealed a group of lncRNAs that exhibit Bcr-Abl-dependent expression. In this study, we focused on lncRNA-X that was downregulated by Bcr-Abl, suggesting that lncRNA-X might have a function of tumor suppression. We showed that lncRNA-X over-expression delays Bcr-Abl-induced tumorigenesis in vivo, maybe through its effect on cell survival by modulating STAT5-dependent expression of anti-apoptotic Bcl-XL protein. We also demonstrated that lncRNA-X may affect tumor formation behavior of Bcr-Abl-transformed cells by regulating signaling pathways associated with leukemia stem cells of CML. Together, these results suggest that lncRNA-X suppresses Bcr-Abl-induced tumorigenesis, and the tumor suppressor function of lncRNA-X may be of significance for exploring novel therapeutic strategies for treating CML. This microarray was performed to identify lncRNAs associated with Bcr-Abl-induced chronic myeloid leukemia (CML).
2015-07-20 | GSE42269 | GEO
Project description:Protein tyrosine phosphorylation (pY) is central to many cellular signaling pathways. Deregulation of pY can lead to malignancies such as leukemia. Thus, assigning kinase-substrate relations is imperative to understand disease alterations. However, such efforts are complicated by kinase redundancy, overlapping specificity and magnitude differences in enzymatic activity. BCR/ABL, the predominant oncogene in leukemia, drives malignant transformation by deregulated tyrosine kinase activity. In this study, phosphorylation activity and specificity of human ABL1 and BCR/ABL have been examined in yeast by state-of-the-art phosphoproteomics. Linear sequence motif scores were generated and used for cross-kingdom (fungi to metazoa) phosphorylation analysis. Phosphoproteomic analysis of ABL1 and BCR/ABL yielded a high-confidence pY-dataset of 1186 peptides covering 1127 sites on 821 proteins. Motif scores generated from this dataset allow for examination of ABL1 and BCR/ABL kinase activity in human cell lines, and clearly identified BCR/ABL p210 in the chronic myeloid leukemia cell line K562. This cross-kingdom approach offers valuable insights into the human phosphoproteome.
2023-07-20 | PXD038551 | Pride
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:To investigate the mechanism of telomerase regulation in BCR-ABL positive cells due to its clinical value, we studied the catalytic component of telomerase, TERT. Our results suggest that BCR-ABL plays an important role in regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was downregulated, therefore suggesting a positive correlation between BCR-ABL and hTERT. Gleevec treatment inhibited hTERT at the mRNA level and significantly reduced telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells. TRAP assay also revealed that Gleevec treatment significantly reduced TA specifically in K562 cells. Furthermore, translocation of hTERT from nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec. Although Gleevec down-regulated hTERT mRNA level, the protein level of hTERT remained unchanged. Therefore, Gleevec-induced-TA decrease is not due to the alteration in telomerase subunits expression. It could be presumably due to posttranslational modification of hTERT, possibly through multiple signaling pathways. We have found that Gleevec reduced the tyrosine phosphorylation of hTERT by BCR-ABL, which is associated with the nucleoplasm localization of hTERT from nucleoli sequesters. These findings reveal unknown functions and regulations of telomerase by BCR-ABL. Using cRNA microarray, gene expression of Gleevec-treated and non-treated K562 (BCR-ABL positive) cells were compared against Gleevec-treated and non-treated HL60 (BCR-ABL deficient) cells.
2011-12-15 | E-GEOD-26821 | biostudies-arrayexpress
Project description:The BCR-ABL oncogene, generated by Philadelphia chromosome, is present in about 95% human Chronic myeloid leukemia (CML) and 20~30% acute lymphoblastic leukemia (ALL). One of BCR-ABL isoforms, P210, is more often detected in CML and ALL patients. Although BCR-ABL kinase inhibitors are effective in controlling the diseases, they do not provide cure due to the development of drug resistance and the insensitivity of leukemia stem cells to these drugs. Identification of new therapeutic targets is critical. To identify potential target against leukemia stem cells, we studied gene expression in leukemia stem cells, which were identified in mice in our lab (Hu Y, Swerdlow S, Duffy TM, Weinmann R, Lee FY, Li S. 2006. Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia. Proc Natl Acad Sci USA 103(45):16870-16875.). The sorted leukemia stem cells that expressed BCR-ABL were used for isolation of RNA, followed by the analysis of gene expression using the DNA microarray. The same lineage of non-BCR-ABL-expressing normal hematopoietic stem cells was used as control. We have identified some interesting genes that are up- or down-regulated by BCR-ABL in these leukemia stem cells. We are currently studying the functions of these identified genes. Keywords: Genetic modification
2008-03-22 | GSE10912 | GEO
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. Total RNA was extracted from K562 cells treated with 0.2% DMSO for 24hrs or 100nM dasatinib for 4hrs, 8hrs, and 24hrs.
2013-09-24 | E-GEOD-51083 | biostudies-arrayexpress
Project description:Chronic myeloid leukemia is a malignant hematopoietic disorder distinguished by a presence of BCR-ABL fused oncogene with constitutive kinase activity. Although targeted therapy by tyrosine kinase inhibitors (TKI) markedly improved patient´s survival and quality of life, development of drug resistance remains a critical issue for a subset of patients. The most common mechanism of TKI resistance in CML patients is a mutation in BCR-ABL gene which makes oncogenic Bcr-Abl protein insensitive to TKI therapy. Mutation independent mechanisms of TKI resistance are less elucidated, but exosomes, extracellular vesicles excreted from normal and tumor cells were recently linked with cancer progression and drug resistance. We used an imatinib-sensitive CML cell line K562 and derived an imatinib-resistant subline K562IR by prolonged cultivation of cells in presence of imatinib. We demonstrated that exosomes isolated from K562IR cells are internalized by K562 cells and increase their survival in presence of 2µM imatinib. To characterize the exosomal cargo and to identify resistance-associated marker proteins, we performed a deep proteomic analysis of exosomes from both cell sublines using label free quantification (LFQ). In total, we identified over 3000 exosomal proteins including 31 proteins differentially abundant in exosomes derived from K562IR cells. Among the differential proteins were three massively upregulated membrane proteins in K562IR exosomes with surface localization: IFITM3, CD146, CD36. We verified the massive upregulation of the three proteins in K562IR exosomes and also in K562IR cells. Using flow cytometry, we further demonstrated potential of CD146 as cell surface marker associated with imatinib resistance in K562 cells.
2024-10-24 | PXD019283 | Pride
Project description:Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell, characterized by the expression of the Bcr-Abl oncogene by leukemic cells. In order to analyze the molecular pathways modulated by Bcr-Abl, we have previously generated an inducible model of Bcr-Abl expression in the murine Ba/F3 cell line based on the Tet-OFF system. In the present study, through a microarray approach applied to cells grown with (Bcr-Abl-expression OFF) or without (Bcr-Abl-expression ON) doxycycline, a tetracycline analogue, we analyzed the gene expression variations upon Bcr-Abl expression.
2005-05-01 | E-GEOD-1429 | biostudies-arrayexpress
Project description:Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell, characterized by the expression of the Bcr-Abl oncogene by leukemic cells. In order to analyze the molecular pathways modulated by Bcr-Abl, we have previously generated an inducible model of Bcr-Abl expression in the murine Ba/F3 cell line based on the Tet-OFF system. In the present study, through a microarray approach applied to cells grown with (Bcr-Abl-expression OFF) or without (Bcr-Abl-expression ON) doxycycline, a tetracycline analogue, we analyzed the gene expression variations upon Bcr-Abl expression. Keywords: repeat sample
2005-05-01 | GSE1429 | GEO