Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA294523 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene expression profiles upon Meis1 knockout in Hoxa9/Meis1-induced AML
| PRJNA218195 | ENA
Project description:Meis1 is found cooperatively activated with Hoxa7/a9 in AML, and it indeed promotes leukemogenic activities of Hoxa9. It is important to identify downstream target genes of Meis1 to understand its cooperative activity with Hoxa9 in leukemogenesis. We used microarrays to detail the global programme of gene expression upon Meis1 knockout. Murine primary bone marrow cells of the Rosa26-Cre-ERT2 knock-in mouse were transformed by retroviral transduction of Hoxa9 and floxed Meis1. The immortalized bone marrow cells were treated with 2 μM of 4-hydroxytamoxifen to delete Meis1 cDNA. Gene expression profiles were compared between the original Hoxa9/Meis1-expressing cells and Meis1 deleted (Hoxa9 only) cells.
2015-01-01 | E-GEOD-50645 | biostudies-arrayexpress
Project description:Pyrydopyrazine A2 induced in vitro the differentiation of leukemic cells (HoxA9-Meis1) into macrophages, we decided to perform a transcriptomic study in order to analyze the GM-CSF pathway regulation. We therefore compared effect with A2 to cells treated with Retinoic acid and D3 Vitamin, a combination known to induce also differentiation of leukemic cells. HoxA9-Meis1 murine AML cells were treated in vitro during 24h, with Pyrydopyrazine( A2) at 3.4μM or a combination of all-trans Retinoic Acid (RA) and 1α-hydroxy-D3 Vitamin (D3V), 10μM each. Gene expression signature was compared to untreated control. One sample was tested for each condition
2015-09-02 | E-GEOD-72635 | biostudies-arrayexpress
Project description:OBJECTIVE: The microRNA miR-155 is upregulated in Hoxa9 and Meis1 leukemia inducing cells (LIC) , and miR-155 accelerates the onset of acute myeloid leukemia (AML) together with Hoxa9 but through largely unknown molecular mechanisms. The impact of miR-155 on accelerated onset of leukemia in the context of Hoxa9 and Meis1 is also unclear. To further resolve this, we performed a gene expression profiling, in the context of Hoxa9 and Meis1 leukemogenesis with miR-155 knocked out. RESULTS: Gene expression profiling of Hoxa9/Meis1 LIC without miR-155 does not delay the onset of AML and the gene expression changes are small
2017-04-27 | GSE80660 | GEO
Project description:Analysis of gene expression profile of Hoxa9/Meis1 leukemia cells 6 days after loss of Jmjd1c. Loss of Jmjd1c induces differentiation and Hoxa9/Meis1 leukemia cells. These results provide insight into the role of Jmjd1c in AML with elelvated expression of Hoxa9.
2016-06-09 | GSE75580 | GEO
Project description:The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feed-forward loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, we show that Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
2017-06-14 | PXD004192 | Pride
Project description:RNA expression changes in HOXA9/MEIS1 leukemia cells
| PRJNA401757 | ENA
Project description:HOXA9/MEIS1 plays a synergistic causative role and overexpresses frequently in acute myeloid leukemia (AML). Hoxa9/Meis1 transgenic murine results in rapid leukemic transformation of primary bone marrow cells. However, murine model is not suitable to perform a high-throughput phenotypic screen in vivo and identify compounds for AML therapy. A transgenic zebrafish overexpresses hoxa9/meis1 need to generate. We have engineered an inducible transgenic line Tg (drl:hoxa9;hsp70:meis1) harboring hoxa9/meis1 under the draculin (drl) promoter. The downregulation of runx1, c-myb, mpx, mfap4, and gata1 in Tg (drl:hoxa9;hsp70:meis1) embryos indicated enforced hoxa9/meis1 perturbs embryonic hematopoiesis. Importantly, adult Tg (drl:hoxa9;hsp70:meis1) develops malignant myeloid disease with an abundance of myeloid precursor cells, anemia, and high mortality after a latency period (~5-months-aged) with comparable to murine model and human AML patients. Genome-wide transcription changes analysis indicated arrested differentiation genes such as gata2b, notch1b, and gfi1ab are upregulated. Leflunomide, inhibitor of enzyme dihydroorotate dehydrogenase (DHODH) which is a potential option for differentiation therapy of AML, relieves defective hematopoiesis in transgenic embryos and larvae. Collectively, we have identified an inducible malignant myeloid disease transgenic zebrafish model similar to AML and provided a unique opportunity for high-throughput in vivo chemical screening for AML therapy and study the related mechanisms.
2022-09-01 | GSE204744 | GEO
Project description:Monocytic leukemia Zinc finger protein (MOZ) is a MYST-type acetyltransferase involved in chromosomal translocation in acute myelogenous leukemia (AML) and myelodysplastic syndrome. MOZ is established as essential for hematopoiesis; however, the role of MOZ in AML has not been addressed. We propose that MOZ is critical for AML development induced by MOZ-TIF2 fusions. Moz-deficient hematopoietic stem/progenitor cells (HSPCs) expressing MOZ-TIF2 could form colonies in vitro but could not induce AML in mice. By contrast, Moz was dispensable for colony formation by HOXA9-transduced cells and AML development caused by HOXA9 and MEIS1, suggesting a specific requirement for MOZ in AML induced by MOZ/MLL-fusions. Expression of the of Meis1, but not Hoxa9, was reduced in Moz-deficient MOZ-TIF2 AML cells. AML development induced by MOZ-TIF2 was rescued by introducing Meis1 into Moz-deficient cells carrying MOZ-TIF2. Meis1 deletion impaired MOZ-TIF2-mediated AML development. Active histone modifications were also severely reduced at the Meis1 locus in Moz-deficient MOZ-TIF2 AML cells. These results suggest that endogenous MOZ is critical for MOZ-fusion-induced AML development and maintains active chromatin signatures at target gene loci.
2022-07-24 | GSE208741 | GEO
Project description:OBJECTIVE: MEIS1, a HOX cofactor, collaborates with multiple HOX proteins, such as HOXA9, to accelerate the onset of acute myeloid leukemia (AML) through largely unknown molecular mechanisms. To further resolve these mechanisms, we conducted a structure-function analysis of Meis1 and gene expression profiling, in the context of Hoxa9 leukemogenesis. RESULTS: We show, in a murine bone marrow transplantation model, that the homeodomain of Meis1 is required for leukemogenic collaboration with Hoxa9. Gene expression profiling of a Hoxa9 preleukemic cell line transduced with wild-type or Meis1 homeodomain mutant reveal deregulation of multiple genes including a set not previously implicated as Meis1 targets. Murine bone marrow cells transduced with Hoxa9-GFP + empty MIY vector were compared to Hoxa9+Meis1 cells or Hoxa9+Meis1 with deleted homeodomain (DHD) cells and cultured for three or four weeks before harvest for miRNA expression array. Four independent experiments were performed for each of the three different conditions included in the study. Cells from all samples were also transplanted into lethally irradiated mice to test for their transforming and leukemic potential.
2016-09-01 | E-GEOD-75272 | biostudies-arrayexpress