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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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PRMT1 interacts with leukemia fusion protein AML1-ETO for activation of transcription and transformation

ABSTRACT: Fusion protein AML1-ETO resulted from t(8;21) translocation is highly related to leukemia development. We have previously shown that the expression of AE9a, a spliced form of AML1-ETO, can rapidly cause leukemia in mouse. To understand how AML1-ETO is involved in leukemia development, we used AE9a leukemia model to identify a novel AE9a interacting proteins PRMT1 (protein arginine methyltransferase 1) from primary leukemic cells expressing AE9a. To examine whether PRMT1 is involved in AE9a-mediated transcription regulation, genome wide gene expression analysis is carried out in hematopoietic cell line K562 (wild type or AE9a expressing) treated with (-) control siRNA or siPRMT1. Wild type or AE9a-expressing K562 cells with control siRNA or siPRMT1 in triplicate

ORGANISM(S): Homo sapiens

SUBMITTER: Dong-Er Zhang

PROVIDER: E-GEOD-28135 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential.

Shia Wei-Jong WJ Okumura Akiko J AJ Yan Ming M Sarkeshik Ali A Lo Miao-Chia MC Matsuura Shinobu S Komeno Yukiko Y Zhao Xinyang X Nimer Stephen D SD Yates John R JR Zhang Dong-Er DE

Blood 20120412 21

Fusion protein AML1-ETO, resulting from t(8;21) translocation, is highly related to leukemia development. It has been reported that full-length AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. We have previously shown that the expression of AE9a, a splice isoform of AML1-ETO, can rapidly cause leukemia in mice. To understand how AML1-ETO is involved in leukemia development, we took advantage of our AE9a leukemia model and sought to identify its interact ...[more]

PMID: 22498736

Similar Datasets

PRMT1 interacts with leukemia fusion protein AML1-ETO for activation of transcription and transformation

Project description:Fusion protein AML1-ETO resulted from t(8;21) translocation is highly related to leukemia development. We have previously shown that the expression of AE9a, a spliced form of AML1-ETO, can rapidly cause leukemia in mouse. To understand how AML1-ETO is involved in leukemia development, we used AE9a leukemia model to identify a novel AE9a interacting proteins PRMT1 (protein arginine methyltransferase 1) from primary leukemic cells expressing AE9a. To examine whether PRMT1 is involved in AE9a-mediated transcription regulation, genome wide gene expression analysis is carried out in hematopoietic cell line K562 (wild type or AE9a expressing) treated with (-) control siRNA or siPRMT1.

2012-06-18 | GSE28135 | GEO

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

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

Genes regulated by AML1/ETO in U937 cells

2008-11-28 | GSE10520 | GEO

AML1-ETO target genes

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

Kasumi-1 AML1-ETO knockdown samples

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

AML1/ETO, AML1, and HEB binding patterns on chromosme 19

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

caArray_stegm-00394: Broad: Identification of AML1-ETO modulators by chemical genomics

Project description:Somatic rearrangements of transcription factors are common abnormalities in the acute leukemias. With rare exception, however, the resultant protein products have remained largely intractable as pharmacologic targets. One example is AML1-ETO, the most common translocation reported in acute myeloid leukemia (AML). To identify AML1-ETO modulators, we screened a small molecule library using a chemical genomic approach. Gene expression signatures were used as surrogates for the expression versus loss of the translocation in AML1-ETO-expressing cells. The top classes of compounds that scored in this screen were corticosteroids and dihydrofolate reductase (DHFR) inhibitors. In addition to modulating the AML1-ETO signature, both classes induced evidence of differentiation, dramatically inhibited cell viability, and ultimately induced apoptosis via on-target activity. Furthermore, AML1-ETO-expressing cell lines were exquisitely sensitive to the effects of corticosteroids on cellular viability compared with nonexpressers. The corticosteroids diminished AML1-ETO protein in AML cells in a proteasome- and glucocorticoid receptor-dependent manner. Moreover, these molecule classes demonstrated synergy in combination with standard AML chemotherapy agents and activity in an orthotopic model of AML1-ETO-positive AML. This work suggests a role for DHFR inhibitors and corticosteroids in treating patients with AML1-ETO-positive disease.

2016-12-08 | GSE91002 | GEO

HDAC3 preferentially binds to RUNX1 in t(8;21) AML cells and collaborates with RUNX1 to repress AML1-ETO-mediated transcriptional activation

Project description:Human histone deacetylase 3 (HDAC3) plays an important role in gene transcription in diseased human cells, such as leukemia. The t(8;21) chromosomal translocation is one of the most commonly observed genetic abnormalities associated with acute myeloid leukemia. This translocation generates the AML1-ETO fusion protein between the wild-type RUNX1 transcription factor and wild-type ETO transcriptional corepressor. To better understand the role of HDAC3 in t(8;21) leukemogenesis, the human HDAC3-containing complexes were isolated from stably-transfected HeLa cells by using anti-FLAG immunoprecipitation. The resulting complexes were resolved in SDS-PAGE. The components of the complexes were identified using LC-MS/MS. We report here that the human RUNX1 transcription is a component of the HDAC3 complexes. We demonstrate that HDAC3 and RUNX1 collaboratively repress AML1-ETO-mediated transcription. These results reveal new insight into how AML1-ETO, RUNX1, and HDAC3 crosstalk to deregulate gene transcription in t(8;21) leukemia cells.

2020-02-17 | PXD017230 | Pride

AML1-ETO and CCND2 overexpression¬ cooperate to drive acute myeloid leukemia initiation and progression

Project description:Increasing numbers of clinical cohorts have detected CCND2 mutations in acute myeloid leukemia (AML), especially in the subtype of AML with t(8;21) translocation. As known, this AML subtype is characterized by the formation of AML1-ETO fusion gene. However, AML1-ETO fusion gene alone is not sufficient to drive leukemia development, additional mutations are required for leukemogenesis. Here, we aim to investigate whether mutated CCND2 can cooperate with AML1-ETO fusion gene to drive leukemia initiation and progression. In our previous study, the conditional AML1-ETO knock-in mouse model (AML1/ETO mouse), which represented a pre-leukemia stage as myeloproliferative neoplasm phenotype, was established. To confirm whether the AML1-ETO and CCND2 mutation can cooperate to drive leukemia, the mice transduction and transplantation model harboring both AML1-ETO and CCND2 gene (both wildtype and mutant) were established. Upon the assessment of the phenotype, biological features and survival of the mice, only the mice overexpressing the AML1-ETO and CCND2 simultaneously were eventually progressed to leukemia. Besides, compared to mice overexpressing AML-ETO gene alone, mTOR and cell cycle-related pathways were significantly enriched in mice harboring both AML1-ETO and CCND2. And the selective mTOR inhibitor, Everolimus, can reduce the leukemia burden and prolong the survival of this group of mice. In conclusion, we confirmed that introduction of the CCND2 gene into the AML/ETO pre-leukemia mice can trigger the development of leukemia. We also confirmed that CCND2 overexpression resulted in the upregulation of the mTOR pathway and inhibiting the pathway may be a therapeutic agent for this subtype of leukemia.

2024-04-19 | GSE263911 | GEO

AML1/ETO binding pattern on human promoters

2008-12-22 | GSE10531 | GEO

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