Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA178211 | ENA |
REPOSITORIES: ENA
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Project description:It has been known that aberrant isoforms of Ikaros family ptoteins are expressed in malignant cells. We identified that PBMC of ATL (acute T-cell leukemia) patients expresses different patterns of Helios isoforms compared with normal PBMC. In order to investigate the biological impact of ATL-type Helios isoform, we conducted complehensive gene expression analyses in Jurkat cells overexpressing ATL-type Helios. Also, we investigated the influence of WT-Helios or WT-Ikaros knockdown on the gene expression profile and compared with that of the cells with ATL-type Helios overexpression.
2013-03-31 | GSE41796 | GEO
Project description:It has been known that aberrant isoforms of Ikaros family ptoteins are expressed in malignant cells. We identified that PBMC of ATL (acute T-cell leukemia) patients expresses different patterns of Helios isoforms compared with normal PBMC. In order to investigate the biological impact of ATL-type Helios isoform, we conducted complehensive gene expression analyses in Jurkat cells overexpressing ATL-type Helios. Also, we investigated the influence of WT-Helios or WT-Ikaros knockdown on the gene expression profile and compared with that of the cells with ATL-type Helios overexpression. Total RNA samples from Jurkat cells were subjected to Cy-3 labeling followed by human whole genome gene expression microarray analyses.
2013-03-31 | E-GEOD-41796 | biostudies-arrayexpress
Project description:In this study, the ectopic overexpressions of the wild-type Helios-1, non-canonical short isoforms Helios-Δ190-1186, Helios-Δ326-1431, and control in the Jurkat cells were utilized as the routine in vitro model of the T-cell acute lymphoblastic leukemia (T-ALL). We compared the microarray data for transcriptional analysis of the Jurkat cells with stable overexpression of full-length Helios-1, non-canonical short isoforms Helios-Δ190-1186, Helios-Δ326-1431, and mock transfected control.
2016-12-15 | GSE92416 | GEO
Project description:Inositol 5-phosphatase SHIP is differentially expressed in Ikaros and Helios deficient cells. In the absense of Ikaros SHIP is upregulated where as in the absense of Helios it is downregulated. Ikaros binds to the promoter of the SHIP gene. Article provides insight into the mechanisms of action Ikaros employs to regulate BCR signaling. Two replicates of Ikaros deficient and wild type DT40 avian B cells.
2010-07-19 | E-GEOD-20946 | biostudies-arrayexpress
Project description:Inositol 5-phosphatase SHIP is differentially expressed in Ikaros and Helios deficient cells. In the absense of Ikaros SHIP is upregulated where as in the absense of Helios it is downregulated. Ikaros binds to the promoter of the SHIP gene. Article provides insight into the mechanisms of action Ikaros employs to regulate BCR signaling.
2010-07-19 | GSE20946 | GEO
Project description:T cell development is accompanied by epigenetic changes that ensure the silencing of stem cell-related, and the activation of lymphocyte-specific programs. How transcription factors influence these changes remains unclear. We show that the Ikaros transcription factor interacts with the Polycomb Repressive Complex 2 (PRC2) in CD4-CD8- thymocytes, and allows its binding to >200 developmentally-regulated genes, many of which are expressed in hematopoietic stem cells. Loss of Ikaros in CD4-CD8- cells leads to diminished histone H3 Lys27 (H3K27) trimethylation and ectopic expression of these genes. Ikaros binding triggers PRC2 recruitment and H3K27 trimethylation. Furthermore, Ikaros interacts with PRC2 independently of the Nucleosome Remodeling and Deacetylation complex. Our results identify Ikaros as a fundamental regulator of PRC2 function in developing T cells. Genome-wide comparison of different histone modifications, Ikaros, Suz12 and NuRD binding in different stages of T cell development in WT and Ikaros mutant mice. Profiling of H3K27me3 in DN1, DN2, DN3, DN4 and DP thymocytes and hematopoietic stem and progenitor cells (LSK cells) of WT and Ikaros mutant mice. Profiling of H3K4me3 and H3ac in WT and Ikaros mutant DP thymocytes. Global analysis of Ikaros binding in WT DN3, DN4 and DP cells, Suz12 binding in WT and Ikaros mutant DN3 cells, and Mta2 and Mi2beta binding in WT DN3 cells. Genome-wide profiling of Ikaros binding and H3K27me3 upon Ikaros activation in Ikaros-deficient leukemic T cells.
2015-11-03 | E-GEOD-61148 | biostudies-arrayexpress
Project description:Adult T-cell lymphoma/leukemia (ATL) is an aggressive subtype of leukemia/lymphoma caused by human T-cell leukemia virus type-1 (HTLV-1) and existing chemotherapy for ATL remains with extremely poor prognosis. Therefore, more effective therapeutic options are urgent needs for this disease. Since recent two clinical studies proved promising curability of Lenalidomide (LEN, a second-generation immunomodulatory drug [IMiDs]) for ATL patients, we investigated the direct growth-inhibitory machineries of LEN on ATL cells. Among 13 ATL-related cell lines, Hut102 and TL-Om1 exhibited best response to LEN treatment and LEN-induced functional modulation of E3-ubiquitin ligase cereblon (CRBN) induced degradation of hematopoietic-specific ikaros-family transcription factors IKZF1 and IKZF3 followed by suppression of their down-stream effectors IRF4 and c-Myc (both have been implied to promote ATL cell malignancy). Additionally, Hut102 and TL-Om1 displayed impaired expression of IKZF2 (deletion in HuT102 and altered translational variants in TL-Om1). LEN-induced growth inhibition to these two cell-lines seemed to be attributed to functional deprivation of all IKZF1/2/3. While CRBN-knockdown (KD) in HuT102 imposed LEN-resistance, IKZF2-KD in LEN-resistant ED40515 induced LEN sensitivity. DNA microarray analysis on LEN-treated HuT102 and OATL4 (LEN-resistant) displayed distinct LEN-responding transcriptional profiles; restoration of immune competency and oncogenic growth promotion respectively. Oral administration of LEN to HuT102-xenographted SCID mice demonstrated significant reduction of tumor mass. Finally, a novel form of IMiDs or cereblon modulator (CELMoD), iberdomide (IBE) exerted deeper and wider range of growth suppression to ATL cells including IKZF2 down regulation. Altogether, these findings strongly indicate the therapeutic advantages of IMiDs or CELMoD against ATL.
2024-02-15 | GSE221062 | GEO
Project description:Adult T-cell lymphoma/leukemia (ATL) is an aggressive subtype of leukemia/lymphoma caused by human T-cell leukemia virus type-1 (HTLV-1) and existing chemotherapy for ATL remains with extremely poor prognosis. Therefore, more effective therapeutic options are urgent needs for this disease. Since recent two clinical studies proved promising curability of Lenalidomide (LEN, a second-generation immunomodulatory drug [IMiDs]) for ATL patients, we investigated the direct growth-inhibitory machineries of LEN on ATL cells. Among 13 ATL-related cell lines, Hut102 and TL-Om1 exhibited best response to LEN treatment and LEN-induced functional modulation of E3-ubiquitin ligase cereblon (CRBN) induced degradation of hematopoietic-specific ikaros-family transcription factors IKZF1 and IKZF3 followed by suppression of their down-stream effectors IRF4 and c-Myc (both have been implied to promote ATL cell malignancy). Additionally, Hut102 and TL-Om1 displayed impaired expression of IKZF2 (deletion in HuT102 and altered translational variants in TL-Om1). LEN-induced growth inhibition to these two cell-lines seemed to be attributed to functional deprivation of all IKZF1/2/3. While CRBN-knockdown (KD) in HuT102 imposed LEN-resistance, IKZF2-KD in LEN-resistant ED40515 induced LEN sensitivity. DNA microarray analysis on LEN-treated HuT102 and OATL4 (LEN-resistant) displayed distinct LEN-responding transcriptional profiles; restoration of immune competency and oncogenic growth promotion respectively. Oral administration of LEN to HuT102-xenographted SCID mice demonstrated significant reduction of tumor mass. Finally, a novel form of IMiDs or cereblon modulator (CELMoD), iberdomide (IBE) exerted deeper and wider range of growth suppression to ATL cells including IKZF2 down regulation. Altogether, these findings strongly indicate the therapeutic advantages of IMiDs or CELMoD against ATL.
2024-02-15 | GSE221056 | GEO
Project description:Immunomodulatory imide drugs (IMiDs), such as thalidomide and its analogues, are some of the most commonly utilized E3 ligase ligands for the development of proteolysis targeting chimeras (PROTACs). While the canonical neo-substrates of IMiDs (i.e., Ikaros and Aiolos) are often considered to be unwanted off-targets of PROTACs, maintaining the degradation of these neo-substrates also provides the opportunity to synergistically degrade multiple proteins with a single compound. Here, we report the development of ALV-07-082-03, a CDK4/CDK6/Helios triple degrader that consists of palbociclib, an FDA-approved CDK4/6 inhibitor, conjugated to DKY709, a novel IMiD-based Helios degrader. Pharmacological co-degradation of CDK4/6 and Helios resulted in potent suppression of downstream signaling and proliferation in cancer cells, as well as enhanced de-repression of IL-2 secretion. Thus, not only do we demonstrate the possibility of rationally re-directing the neo-substrate specificity of PROTACs by incorporating alternative molecular glue molecules as E3 ligase ligands, but our findings also suggest that co-targeting CDK4/6 and Helios may have synergistic effects.
2022-09-07 | PXD036170 | Pride
Project description:The LEDGF transcript from the PSIP1 gene was knocked down in Jurkat cells using RNAi technology. The resulting Jurkat-derived cell line (Jurkat-siJK2) was compared to a control cell line (wild type Jurkat) using microarray analysis. Genes identified as being modulated by LEDGF were preferential targets of HIV integration. Keywords: effects of gene knockdown
2007-04-13 | GSE7508 | GEO