GFI1 is pivotal for AML1-ETO positive acute myeloid leukemia
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ABSTRACT:
PROVIDER: PRJNA400629 | ENA |
REPOSITORIES: ENA
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Project description:AML1-ETO (Acute Myeloid Leukemia 1-Eight Twenty One) caused by the translocation t(8;21)(q22;q22) is a mutated transcription factor contributing to AML development. Although associated with a favorable prognosis, half of the patients fail to achieve long-term survival. We examined the role of the transcription factor Growth factor independence 1 (GFI1) in the initiation and progression of leukemia and exploited the use of a drug targeting GFI1 expression in the context of AML1-ETO associated AML. We could show that GFI1 is required for maintenance of AML1-ETO associated leukemia and that loss of GFI1 or targeting GFI1 expression impedes leukemia initiation and progression and could be a potential new therapeutic strategy for patients failing to respond to chemotherapy.
2018-07-13 | GSE103255 | GEO
Project description:U937 AML cells that express an inducible AML1-ETO construct under the control of the tetracycline promoter. Microarrays used to discover an AML1-ETO signature for a GE-HTS screen to identify AML1-ETO modulators.
2009-05-01 | GSE15647 | GEO
Project description:The AML1/ETO fusion protein is essential to the development of acute myeloid leukemia (AML), and is well recognized for its dominant-negative effect on the co-existing wild-type protein AML1. However, the involvement of wild-type AML1 in AML1/ETO-driven leukemogenesis remains elusive. Through chromatin immunoprecipitation sequencing, computational analysis plus a series of experimental validations, we report here that AML1 is able to orchestrate the expression of AML1/ETO targets regardless of being activated or repressed, via forming a complex with AML1/ETO and via recruiting the cofactor. 4 ChIP-seq assays were used to identify the high confidence binding regions of AML1-ETO and AML1 in t(8;21) AML Kasumi-1 cell lines. The anti-AML1 (N20) antibody targets the N-terminus of AML1 and recognizes both AML1 and AML1/ETO; the anti-AML1 (C19) antibody targets the C-terminus of AML1 and recognizes AML1 but not AML1/ETO; the anti-ETO (C20) antibody targets the C-terminus of ETO and specifically recognizes AML1/ETO. 2 ChIP-seq assays were used to identify the binding regions of AML1 in human macrophage U937 cell lines. And the total input was used as control.
2015-11-04 | E-GEOD-65427 | biostudies-arrayexpress
Project description:human CD34 cells isolated from cord blood or peripheral blood transduced with AML1-ETO or Empty vector (MIGR1) Keywords = AML1-ETO Leukemia Keywords: repeat sample
2005-03-01 | GSE2049 | GEO
Project description:The AML1/ETO fusion protein is essential to the development of acute myeloid leukemia (AML), and is well recognized for its dominant-negative effect on the co-existing wild-type protein AML1. However, the involvement of wild-type AML1 in AML1/ETO-driven leukemogenesis remains elusive. Through chromatin immunoprecipitation sequencing, computational analysis plus a series of experimental validations, we report here that AML1 is able to orchestrate the expression of AML1/ETO targets regardless of being activated or repressed, via forming a complex with AML1/ETO and via recruiting the cofactor.
2015-11-04 | GSE65427 | GEO
Project description:In an effort to identify novel drugs targeting fusion-oncogene induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE) driven AML we uncovered a deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein which is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem- and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO positive leukemic stem cells.
2021-11-04 | PXD026374 | Pride
Project description:Kasumi-1 AML cells that were transfected in triplicate with AML1-ETO or luciferase siRNA constructs by either Amaxa nucleofection or Biorad siLentFect and incubated for 96 hours. Microarrays used to discover an AML1-ETO signature for a GE-HTS screen to identify AML1-ETO modulators.
2009-05-01 | GSE15646 | GEO
Project description:MEIS2 collaborates with AML1-ETO in inducing acute myeloid leukemia in a murine bone marrow transplantation model We compared Gene expression profile (GEP) of murine bone marrow cells transduced with GFP, AML1-ETO, MEIS2, and AML1-ETO/MEIS2. Data from MEIS1 and AML1-ETO/MEIS1 is also included. Mouse bone marrow cells were kept in culture for 48hrs after retroviral transduction. GFP positive cells were then sorted and cells were kept for further 24 hours in culture before microarray analysis.
2016-07-04 | E-GEOD-81174 | biostudies-arrayexpress
Project description:Compare the gene expression profile among human CD34+ cord blood cells infected with MIGR1, MIGR1-AML1-ETO or MIGR1-AML1-ETO∆NHR1 AML1-ETO promotes the self-renewal of human hematopoietic stem/progenitor cells (HSPCs). We found deletion of NHR1 domain abrogates AML1-ETO induced expasion of HSPCs.
2011-07-19 | GSE28317 | GEO
Project description:Approximately 20% of Acute Myelogenous Leukemia (AML) cases carry the t(8;21) translocation, which involves the AML1 and ETO genes, and express the resulting AML1/ETO fusion protein that functions as a transcriptional repressor by recruiting NCoR/SMRT/HDAC complexes to DNA. We used ChIP-chip to identify the determinants of AML1/ETO binding on a contiguous DNA region (chromosome 19). AML1/ETO binding regions are characterized by a specific sequence signature that includes the presence of the consensus binding sites for the AML1 and HEB transcription factors. We therefore assessed the binding patterns of AML1 and HEB on chromosome 19. A specific chromatin modification (tri-methylation of lysine 4 on histone 3 = 3MetK4) was also studied in U937 cells expressing AML1/ETO in order to correlate the identified binding profiles with active transcription sites. Keywords: ChIP-chip
2008-11-28 | GSE10578 | GEO