Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA107693 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We studied the chromatin modification patterns induced by the presence of the MLL-AF9 fusion protein in a model of human hematopoietic stem/progenitor cells (HSPC) transduced with retrovirus expressing MLL-AF9cDNA (HSPC-MA9). Comparative ChIP-seq analysis between HSPC-MA9 and control HSPC, revealed a massive hyperacetylation of histones that was consistent with the transcriptional profile in the presence of MLL-AF9 fusion protein. Furthermore, we identified 66 MLL-AF9 targets, and found that H4ac was present along with H3K4me3 and H3K79me2 chromatin marks in over 50% of the MLL-AF9 target genes. Examination of histone aceylation and methylation changes upon expression of MLL-AF9 fusion protein in human hematopoietic stem/progenitor cells.
2015-03-01 | E-GEOD-54344 | biostudies-arrayexpress
Project description:We investigated early changes of gene expressions and chromatin accessibilities in hematopoietic stem and progenitor cells (HSPCs) in response to MLL-AF9 oncogene expressions. Using RNA-Seq and ATAC-Seq, we analyzed HSPCs briefly exposed to MLL-AF9 for one or two days. Such analysis addressed the initial changes during malignant transformation, and provided insights into the primary functions of MLL-AF9 oncogene.
2019-10-12 | GSE121768 | GEO
Project description:Using ChIP-seq we examined the occupancy changes of various histone marks and chromatin-bound proteins following accute MLL-AF9 degradation in MLL-AF9-HA-FKPB12 transformed human (HCB1) cells. We also examined occupancy changes of various chromatin-bound proteins in human MLL-AF9-HA-FKBP12 transformed cells (HCB1) and MOLM13 cells in response to DOT1L inhibition, Menin-MLL inhibition, and the combination of DOT1L and Menin-MLL inhibition.
2022-03-03 | GSE173599 | GEO
Project description:This study report that miR-150, a key hematopoietic regulatory microRNA (miRNA) and one of the most downregulated miRNAs in MLL-associated leukemias, acts as a tumor suppressor to block the leukemogenic potency of leukemic stem cells. When expression of miR-150 was restored, a significantly suppressed leukemic stem cell potency of MLL-AF9 cells was observed both in vivo and in vitro. To investigate the tumor suppressive function of miR-150 in MLL-AF9 cells, we isolated three batches of MLL-AF9 cells infected with MDH empty vector or MDH-miR-150 expression retrovirus. Total RNA were extracted and applied for Agilent array analysis. Gene profiling analysis demonstrated that elevated miR-150 altered various aspects of gene expression patterns in MLL-AF9 cells, including stem cell signatures, cancer pathways, and cell survival. miR-150-MLL-AF9 and MDH-MLL-AF9 isolated cells were compared for gene expression patterns. Triplicates using three batches of FACS sorted cells were compared in pairs on the array. MDH-MLL-AF9 samples were labeld with Cy3 and miR-150-MLL-AF9 samples were labled with Cy5.
2011-07-19 | E-GEOD-30771 | biostudies-arrayexpress
Project description:To explore oncogene addiction programs in a genetically defined leukemia context we developed an AML mouse model driven by a conditional MLL-AF9 allele together with oncogenic Ras, which enabled us to examine the consequences of MLL-AF9 inhibition in established disease. In order to produce a tightly regulated system that was easy to monitor, we constructed two retroviral vectors containing dsRed-linked MLL-AF9 under control of a tetracycline response element promoter, and KrasG12D or NrasG12D linked to the “Tet-off” tet-transactivator, which activates TRE expression in a doxycycline repressible manner. Leukemias were generated by retroviral cotransduction of both vectors into hematopoietic stem and progenitor cells, which were transplanted into syngeneic mice. Cells harboring both constructs induced aggressive myelomonocytic leukemia. Five independent primary leukemia cell lines were established from bone marrow of terminal mice. Treatment of these lines with doxycycline rapidly turned off MLL-AF9 expression, and induced terminal myeloid differentiation and complete disease remission in vivo. To identify molecular mechanisms underlying addiction to MLL-AF9, we analyzed global gene expression changes following doxycycline-induced suppression of MLL-AF9.
2011-08-05 | GSE30746 | GEO
Project description:To explore oncogene addiction programs in a genetically defined leukemia context we developed an AML mouse model driven by a conditional MLL-AF9 allele together with oncogenic Ras, which enabled us to examine the consequences of MLL-AF9 inhibition in established disease. In order to produce a tightly regulated system that was easy to monitor, we constructed two retroviral vectors containing dsRed-linked MLL-AF9 under control of a tetracycline response element promoter, and KrasG12D or NrasG12D linked to the “Tet-off” tet-transactivator, which activates TRE expression in a doxycycline repressible manner. Leukemias were generated by retroviral cotransduction of both vectors into hematopoietic stem and progenitor cells, which were transplanted into syngeneic mice. Cells harboring both constructs induced aggressive myelomonocytic leukemia. Five independent primary leukemia cell lines were established from bone marrow of terminal mice. Treatment of these lines with doxycycline rapidly turned off MLL-AF9 expression, and induced terminal myeloid differentiation and complete disease remission in vivo. To identify molecular mechanisms underlying addiction to MLL-AF9, we analyzed global gene expression changes following doxycycline-induced suppression of MLL-AF9. Independent primary acute myeloid leukemia lines induced by cotransduction of Tet-off MLL-AF9 together with either KrasG12D or NrasG12D were grown in culture and treated with doxycycline for 6 days to inactivate MLL-AF9 expression. In addition, primary acute myeloid leukemia lines with constitutive MLL-AF9 and KrasG12D were included to control for the effects of doxycycline. Untreated and treated cells were harvested for RNA extraction and hybridization to Affymetrix arrays.
2011-08-04 | E-GEOD-30746 | biostudies-arrayexpress
Project description:We investigated the response of acute myeloid cells (AML) expressing MLL-AF9 fusion gene to the pan-HDACi panobinostat (LBH589), and found that low conentrations of panobinostat lead to MLL-AF9 cell toxicity and rapid changes in gene expression. Human hematopoietic stem/progenitor cells (HSPC) expressing MLL-AF9 fusion protein (Wei et al, Cancer Cell 2008) were cultured with 30 nM panobinostat during 6 and 24 hours. The different gene expression between cells treated and untreated was studied by gene expression analysis.
2015-03-01 | GSE54218 | GEO
Project description:This study report that miR-150, a key hematopoietic regulatory microRNA (miRNA) and one of the most downregulated miRNAs in MLL-associated leukemias, acts as a tumor suppressor to block the leukemogenic potency of leukemic stem cells. When expression of miR-150 was restored, a significantly suppressed leukemic stem cell potency of MLL-AF9 cells was observed both in vivo and in vitro. To investigate the tumor suppressive function of miR-150 in MLL-AF9 cells, we isolated three batches of MLL-AF9 cells infected with MDH empty vector or MDH-miR-150 expression retrovirus. Total RNA were extracted and applied for Agilent array analysis. Gene profiling analysis demonstrated that elevated miR-150 altered various aspects of gene expression patterns in MLL-AF9 cells, including stem cell signatures, cancer pathways, and cell survival.
2011-07-20 | GSE30771 | GEO
Project description:The MLL gene is a common target of chromosomal translocations found in human leukemia. MLL-fusion leukemias are consistently poor prognosis. One of the most common translocation partners is AF9 (a.k.a. MLLT3). MLL-AF9 recruits DOT1L, a histone 3 lysine 79 methyltransferase (H3K79me1/me2/me3), leading to aberrant gene transcription. We show that DOT1L has three AF9 binding sites, and present the NMR solution structure of a DOT1L-AF9 complex. We generated structure-guided point mutations with graded effects on recruitment of DOT1L to MLL-AF9. ChIP-Seq analyses of H3K79me2 and H3K79me3 show that graded reduction of the DOT1L interaction with MLL-AF9 results in selective losses in H3K79me2 and me3 marks at MLL-AF9 target genes. Furthermore, the degree of DOT1L recruitment defines the level of MLL-AF9 hematopoietic transformation. Hematopoietic progenitor cells isolated from mouse bone marrow were transduced with retrovirus expressing either wildtype MLL-AF9 (WT), mutants, MLL-AF9 (D544R) and MLL-AF9 (D546R). ChIP-Seq analyses were performed on these wildtype and mutant cells using H3K79me2 and H3K79me3 antibodies. 3 samples corresponding to ChIP-Seq with H3K79me2 antibody: 1) MLL-AF9 (WT) 2) MLL-AF9 (D544R) 3) MLL-AF9 (D546R) 3 Samples Corresponding to ChIP-Seq with H3K79me3 antibody: 4) MLL-AF9 (WT) 5) MLL-AF9 (D544R) 6) MLL-AF9 (D546R)
2015-04-30 | E-GEOD-64365 | 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. 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