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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Targeting Csnk1a1 induces selective p53-dependant killing of leukemia stem cells

ABSTRACT: We found found that casein kinase 1 alpha (Csnk1a1), a serine threonine kinase and negative regulator of beta catenin, is essential for leukemia cells in vivo. We examined the effect of Csnk1a1 knowckdown by gene expression profiling in primary leukemia cells.

ORGANISM(S): Mus musculus

SUBMITTER: Fatima Al-Shahrour

PROVIDER: E-GEOD-52928 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Targeting Csnk1a1 induces selective p53-dependant killing of leukemia stem cells

Project description:We found found that casein kinase 1 alpha (Csnk1a1), a serine threonine kinase and negative regulator of beta catenin, is essential for leukemia cells in vivo.

2014-02-23 | GSE52928 | GEO

In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling

Project description:Primary leukemia stem cells (LSCs) reside in an in vivo microenvironment that supports the growth and survival of malignant cells. We used an in vivo short hairpin RNA (shRNA) screening approach to identify novel genes that are essential for primary murine MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is selectively essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation. In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation in long term transplantation assays. We explored the signaling pathways downstream of Itgb3 using an additional in vivo shRNA screen and identified Syk as a critical mediator of Itgb3 activity in leukemia. Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using the Itgb3 knockout mouse model. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML, and demonstrate the utility of in vivo RNA interference screens. We examined the effect of Itgb3 knockdown by gene expression profiling in primary leukemia cells.

2013-04-24 | E-GEOD-46307 | biostudies-arrayexpress

Identification of genes that may predict response to azacitidine treatment.

Project description:Azacitidine (AZA) is a hypomethylating drug used to treat disorders associated with myelodysplasia and related neoplasms. Approximately 50% of patients do not respond to AZA and have very poor outcomes. It is of great interest to identify predictive biomarkers for AZA responsiveness. Therefore, we searched for specific genes whose expression level was associated with response status.Using microarrays, we analyzed gene expression patterns in bone marrow CD34+ cells from 32 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes before AZA therapy. Total RNA was isolated from bone marrow CD34+ cells obtained from myelodysplasia and related neoplasms patients who underwent treatment with 5-azacytidine (AZA, Vidaza). Using Illumina Human HT-12 v. 4 microarrays, we assayed gene expression profiles in patient CD34+ cells before AZA treatment in order to collect basic data for search for markers of the prediction of therapy response.

2016-02-10 | E-GEOD-77750 | biostudies-arrayexpress

Microarray gene expression analysis of T-cell prolymphocytic leukemia (T-PLL) patient samples

Project description:T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. To characterize the gene expression profiles, 12 T-PLL MNC samples (>90% tumor cell content) were screened with Illumina gene expression arrays (Human HT‐12 v4 rev.2 Expression Beadchips).

2017-09-08 | E-MTAB-5916 | biostudies-arrayexpress

Griffiths JAK ESC

Project description:Transcriptional profiling comparison of mouse embryonic stem cells versus their JAK mutated counterparts, cultured both in the presence and absence of LIF (leukemia inhibitory factor).

2011-04-18 | E-MTAB-416 | biostudies-arrayexpress

Transcriptional Profiling of Human Placentas from Pregnancies Complicated by Preeclampsia Reveals Disregulation of Sialic Acid Acetylesterase and Immune Signaling Pathways

Project description:The placenta plays an important role as a regulator of fetal nutrition and growth throughout development and placental factors contribute to gestational abnormalities such as preeclampsia. This study describes the genome-wide gene expression profiles of a large (n=60) set of human placentas in order to uncover gene expression patterns associated with preeclampsia. In addition to confirming changes in expression of soluble factors associated with preeclampsia such as sFLT1 (soluble fms-like tyrosine kinase-1), sENG (soluble endoglin), and INHA (inhibin alpha), we also find changes in immune-associated signaling pathways, offering a potential upstream explanation for the shallow trophoblast invasion and inadequate uterine remodeling typically observed in pathogenesis of preeclampsia. Notably, we also find evidence of preeclampsia-associated placental upregulation of sialic acid acetylesterase (SIAE), a gene functionally associated with autoimmune diseases. 23 preeclamptic, and 37 control placentas included in this study were collected during the years of 2004-2008 and hybridized in two batches to microarrays. Samples were randomized across arrays to control for array and batch variability.

2010-12-10 | E-GEOD-25906 | biostudies-arrayexpress

CK1 Delta Is an mRNA Cap-Associated Protein That Drives Translation Initiation and Tumor Growth

Project description:We perform expression analysis on lymphoma cell lines Z-138 and OCI-Ly10 treated with a novel Casein Kinase 1 delta inhibitor SR-3029

2020-03-13 | GSE146851 | GEO

Monopolar attachment of sister kinetochores at meiosis I requires casein kinase 1.

Project description:The segregation of maternal centromeres away from the paternal ones during the first division of meiosis depends on the attachment of sister kinetochores to microtubules emanating from the same spindle pole. In budding yeast monopolar attachment requires the recruitment to kinetochores of a protein complex called monopolin. The biochemical function of monopolin was unknown. Here, we have identified the casein kinase I Hrr25 as a hitherto unknown subunit of monopolin. Hrr25 differs from other monopolin components by its enzymatic activity and strong evolutionary conservation. We demonstrate that Hrr25’s kinase activity and its interaction with monopolin are both required for monopolar attachment. Accordingly, Hrr25 is associated with centromeres in meiosis I. Our results revealed a surprising new role for casein kinases and provide a hypothesis for the mechanism of monopolar attachment during meiosis I in sexually reproducing organisms: casein kinase I-dependent phosphorylation of kinetochore proteins. Keywords: ChIP-chip, Meiosis, Cell cycle, Saccharomyces cerevisiae, Chromosome VI tiling array, Hrr25, Mam1

2006-09-23 | GSE4792 | GEO

PRMT1 and CSNK1a1 control epidermal progenitor maintanence (PRMT1 ChIP-seq data set)

Project description:Here we determine the genome-wide binding sites of PRMT1 in primary human keratinocytes. We also investigated the impact of casein kinase inhibitor D4476 on PRMT1 genomic binding.

2018-02-02 | GSE110050 | GEO

FACT, PAF-C, and CKII

Project description:Protein-protein interaction analysis for RNA Polymerase II and its elongation factors including: the PAF Complex, the FACT Complex, casein kinase II, DSIF, and TFIIF. These studies also characterized a number of casein kinase II phosphorylation sites on the subunits of the PAF Complex.

2015-07-20 | MSV000079197 | MassIVE

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