Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA94653 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MLL-AF9 transforms committed progenitors to leukemia stem cells by activation of a stem cell program
| PRJNA93883 | ENA
Project description:MLL-AF9 transforms committed progenitors to leukemia stem cells by activation of a stem cell program (expt 2)
| PRJNA93877 | ENA
Project description:MLL-AF9 transforms committed progenitors to leukemia stem cells by activation of a stem cell program (expt 1)
| PRJNA93875 | ENA
Project description:The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined. In a study of target cells and oncogene dosage, we found that Mll-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin- Sca1+ c-kit+) stem cells while committed granulocyte-monocyte progenitors (GMPs) were transformation-resistant and did not cause leukemia. Mll-AF9 was expressed at higher levels in hematopoietic stem (HSC) than GMP cells. Mll- AF9 gene dosage effects were directly shown in experiments where GMPs were efficiently transformed by the high dosage of Mll-AF9 resulting from retroviral transduction. Mll-AF9 up-regulated expression of 196 genes in both LSK and progenitor cells, but to higher levels in LSKs than in committed myeloid progenitors. Experiment Overall Design: Comparison of gene expression profiles among four types of hematopoietic cells (GMP, CMP, CLP and HSC), FACS sorted from wild type and Mll-AF9 knock-in mice. The goal was to identify genes differentially expressed in each Mll-AF9 cell type compared to the corresponding wild type cells.
2008-04-07 | E-GEOD-10627 | biostudies-arrayexpress
Project description:The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined. In a study of target cells and oncogene dosage, we found that Mll-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin- Sca1+ c-kit+) stem cells while committed granulocyte-monocyte progenitors (GMPs) were transformation-resistant and did not cause leukemia. Mll-AF9 was expressed at higher levels in hematopoietic stem (HSC) than GMP cells. Mll- AF9 gene dosage effects were directly shown in experiments where GMPs were efficiently transformed by the high dosage of Mll-AF9 resulting from retroviral transduction. Mll-AF9 up-regulated expression of 196 genes in both LSK and progenitor cells, but to higher levels in LSKs than in committed myeloid progenitors. Keywords: mutant hematopoietic cells
2008-02-25 | GSE10627 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE36346: The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (ChIP-Seq data) GSE36347: The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (expression data) Refer to individual Series
2012-03-28 | E-GEOD-36348 | biostudies-arrayexpress
Project description:The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in MLL-AF9 AML. We evaluated the dependance on beta-catenin for KrasG12DMLL-AF9 leukemia. Lin-Kit+ bone marrow cells obtained from mice transplanted with primary MLL-AF9 leukemia cells and KRasG12DMLL-AF9 leukemia cells were assessed for gene expression in the presence or absence of beta-catenin
2014-07-02 | E-GEOD-49248 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML) with rearrangement of the mixed-lineage leukemia (MLL) gene are the most aggressive hematopoietic malignancies. Previous studies demonstrated the distribution of several epigenetic modifications including H3K9me3, H3K79me2, H3K36me3, H3K4me3 and H3K27me3, in MLL-AF9 transformed murine cells. Here, we examined the H3K9me3 distribution in c-Kit+ cells (enriched with stem/progenitor cells) from both MLL-AF9 transformed murine cells in parallel with control wild-type cells, and found an overall lower distribution of H3K9me3 in leukemia stem cells than normal hematopoietic stem/progenitor cells.
2020-12-22 | GSE132175 | GEO
Project description:Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and apoptosis. In vitro and in vivo pharmacologic targeting of KDM1A using tranylcypromine analogues active in the nanomolar range phenocopied Kdm1a knockdown in both murine and primary human AML cells exhibiting MLL translocations. By contrast, the clonogenic and repopulating potential of normal hematopoietic stem and progenitor cells was spared. Our data establish KDM1A as a key effector of the differentiation block in MLL leukemia which may be selectively targeted to therapeutic effect. To investigate the effects of Kdm1a KD on histone modifications, we performed chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq) in control and Kdm1a KD MLL-AF9 AML cells for dimethyl-H3K4 and dimethyl-H3K9, as well as for trimethyl-H3K4 and trimethyl-H3K9. Dimethyl-H3K4 and dimethyl-H3K9 are targeted for demethylation by KDM1A. For each of these histone modifications, we compared the mean ChIP-Seq signal across and around protein coding genes bound by the MLL-AF9 oncoprotein (Bernt et al., 2011) with the mean signal from genes not bound by MLL-AF9 expressed at high, middle or low levels.
2012-03-28 | E-GEOD-36346 | biostudies-arrayexpress
Project description:The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer. Experiment Overall Design: Samples are from five separate cohorts of mice where leukemia was initiated using distinct MLL fusion oncogenes: MLL-AF1p (n=9), MLL-AF10 (n=8), MLL-GAS7 (n=5), MLL-AF9 (n=5) and MLL-ENL (n=7). Four normal BM samples were also used as controls.
2009-02-21 | E-GEOD-13690 | biostudies-arrayexpress