Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA125111 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Acute myeloid leukemia (AML) is a heterogeneous disease in respect of molecular aberrations and prognosis. We used gene expression profiling of 562 patients treated in the German AMLCG 1999 trial to develop a gene signature that predicts survival in AML. Analysis of 562 samples (140 HGU-133plus2; 422 HGU-133A; 422 HGU-133B) from adult patients with acute myeloid leukemia (AML).
2013-02-07 | E-GEOD-37642 | biostudies-arrayexpress
Project description:Acute Myeloid Leukemia (AML) is commonly associated with alterations in transcription factors due to altered expression or gene mutations. These changes might induce leukemia specific patterns of histone modifications. We used ChIP-Chip to analyze histone H3 Lysine 9 trimethylation (H3K9me3) patterns in primary AML (n=108), ALL (n=28), CD34+ cells (n=21) and white blood cells (n=15) specimens. Hundreds of promoter regions in AML showed significant alterations in H3K9me3 levels. H3K9me3 deregulation in AML occurred preferentially as a decrease in H3K9me3 levels at core promoter regions. The altered genomic regions showed an overrepresentation of cis-binding sites for ets and c-AMP response elements (CREs) for transcription factors of the CREB/CREM/ATF1 family. The decrease in H3K9me3 levels at CREs was associated with increased CRE-driven promoter activity in AML blasts in vivo. AML specific H3K9me3 patterns were not associated with known cytogenetic abnormalities. But a signature derived from H3K9me3 patterns predicted event free survival in AML patients. Combination of the H3K9me3 signature with established clinical prognostic markers outperformed prognosis prediction based on clinical parameters alone. These findings demonstrate widespread changes of H3K9me3 levels at gene promoters in AML. Signatures of histone modification patterns are associated with patient prognosis in AML.
2010-08-22 | GSE20452 | GEO
Project description:Acute myeloid leukemia (AML) is a heterogeneous disease in respect of molecular aberrations and prognosis. We used gene expression profiling of 562 patients treated in the German AMLCG 1999 trial to develop a gene signature that predicts survival in AML.
2013-02-07 | GSE37642 | GEO
Project description:Acute myeloid leukemia (AML) is a malignant disorder of hematopoietic stem cells (HSPCs) where normal 3D genome architectures are essential for proper lineage-specific functions. Repressive epigenetic features, such as Histone 3 Lysine 9 trimethylation (H3K9me3), play vital roles in maintaining healthy HSPCs, but we still understand very little about their roles in promoting AML. Marking constitutive heterochromatin, H3K9me3 is deposited by methyltransferases and participates in heterochromatin condensation; however, its significance in myeloid 3D genome architecture remains unclear. I identified SUV39H1, a key H3K9-specific methyltransferase, as a major depositor in AML cells, essential for sustaining proliferation and myeloid differentiation gene signatures. Moreover, in AML cells treated with DNA hypomethylating agents (HMAs), alterations in H3K9me3 distribution are observed. This suggests a potential role of SUV39H1, the major H3K9me3 depositor, in heterochromatin reorganization in the context of DNA hypomethylation.
2026-06-30 | PXD080372 | Pride
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:The key myeloid transcription factor (TF) CEBPA is frequently mutated in acute myeloid leukemia (AML), but the molecular ramifications of this leukemic driver mutation remain elusive. To investigate CEBPA mutant AML, we compared gene expression changes in human CEBPA mutant AML and in the corresponding CebpaLp30 mouse model, and identified a conserved cross-species transcriptional program. ChIP-seq revealed aberrantly activated enhancers, exclusively occupied by the leukemia-associated CEBPA-p30 isoform. One leukemic-enhancer upstream of Nt5e, encoding CD73, was physically and functionally linked to this conserved AML gene, and could be activated by CEBPA. Targeting of CD73-adenosine signaling increased AML survival in transplanted mice. Our data indicate a first-in-class link between a TF cancer driver mutation and a druggable, direct transcriptional target.
2019-08-08 | PXD011359 | Pride
Project description:The splicing factor RBM25 controls MYC activity in Acute Myeloid Leukemia
| PRJNA454907 | ENA
Project description:Identification of CD84 as a potent survival factor in acute myeloid leukemia
| PRJNA1215696 | ENA
Project description:Acute myeloid leukemia (AML) is driven by a combination of genetic alterations and non-mutational mechanisms that disrupt normal hematopoiesis and support leukemic cell survival. While the mutational landscape of AML is well characterized, the non-genetic processes that sustain leukemic maintenance remain comparatively less understood. Here, we identify BCL2-associated transcription factor 1 (BCLAF1) as a key regulator of mRNA metabolism in AML. BCLAF1 physically associates with core spliceosome components and controls alternative splicing, with a predominant effect on intron retention. We demonstrate that BCLAF1 is required for the productive splicing of activating transcription factor 4 (ATF4) mRNA, thereby sustaining ATF4 protein expression. Loss of BCLAF1 reduces ATF4 protein levels, leading to downregulation of amino acid metabolic target genes essential for leukemic cell survival. Consistently, BCLAF1 deletion compromises ATF4 expression and impairs leukemic progression in mouse models. Moreover, analysis of patient cohort samples reveals a strong correlation between BCLAF1 and ATF4 expression. Together, these findings uncover a previously unrecognized role for BCLAF1 in coordinating mRNA splicing and metabolic adaptation in AML, highlighting its potential as a therapeutic target.
2026-07-29 | PXD065945 | Pride