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Pediatric AML classification according to C/EBPδ expression

ABSTRACT: We examined if pediatric AMLs rank-ordered according to C/EBPδ expression showed the activation of similar pathways. AML samples were dichotomized into groups including the upper quartile (Q1) and the lower three quartiles (Q2-4) according to their C/EBPδ expression values. Moreover, AML samples were associated to French-American-British (FAB) classification.

ORGANISM(S): Homo sapiens

PROVIDER: GSE75461 | GEO | 2016/06/21

SECONDARY ACCESSION(S): PRJNA304350

REPOSITORIES: GEO

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Homo sapiens

Project description:Pediatric AML classification according to C/EBPδ expression

| PRJNA304350 | ENA

Hypoxia limits the tumor-suppressive effects of C/EBPδ in pancreatic cancer

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a horrid disease with a terrifyingly low 5- year survival rate of only 12%. While this rate has slightly increased over the past decade, the incidence of PDAC has risen faster, by about 1% every year. Pre-clinical models are being employed with the aim to better understand the underlying tumor biology but sadly, a translation into the clinic often fails due to unforeseen complications. In a previous study, we showed that the transcription factor C/EBPδ has tumor-suppressive effects on PDAC cells in vitro. In this study, we take those findings a step further and assess the effect of C/EBPδ in a preclinical PDAC model in mice. We establish that the lack of oxygen in vivo – hypoxia - counteracts the tumor-suppressive effects of C/EBPδ in PDAC cells and suggest that this is partly mediated by a reciprocal feedback loop between C/EBPδ and HIF-1α. Although RNA-sequencing shows that the tumor-suppressive effects of C/EBPδ are not entirely abrogated under hypoxia, our study demonstrates the importance of considering major physiological parameters in order to make clinically relevant propositions.

2024-09-18 | GSE226038 | GEO

C/EBPδ drives key endocrine signals in human fetal membranes at parturition

Project description:Amnion-derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of the common transcription factor driving the expression of both cyclooxygenase-2 (COX-2) and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), the key enzymes in their production, may hold the key to the treatment of pre- and post-term labor. Here, we have found that the CCAAT enhancer binding protein δ (C/EBPδ) is such a transcription factor which underlies the feed-forward induction of COX-2 and 11β-HSD1 expression by their own products PGE2 and cortisol in human amnion fibroblasts so that their production would be ensured in the amnion for the onset of labor. Moreover, the abundance of C/EBPδ in amnion increases along with COX-2 and 11β-HSD1 at term and further increases at parturition. Knockout of C/EBPδ in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPδ may serve as a novel pharmaceutical target in the amnion for treatment of pre- and post-term labor.

2021-07-15 | GSE166320 | GEO

C/EBPδ drives key endocrine signals in human fetal membranes at parturition [ChIP-seq]

Project description:Amnion-derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of the common transcription factor driving the expression of both cyclooxygenase-2 (COX-2) and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), the key enzymes in their production, may hold the key to the treatment of pre- and post-term labor. Here, we have found that the CCAAT enhancer binding protein δ (C/EBPδ)is such a transcription factor which underlies the feed-forward induction of COX-2 and 11β-HSD1 expression by their own products PGE2 and cortisol in human amnion fibroblasts so that their production would be ensured in the amnion for the onset of labor. Moreover, the abundance of C/EBPδin amnion increases along with COX-2 and 11β-HSD1 at term and further increases at parturition. Knockout of C/EBPδ in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPδmay serve as a novel pharmaceutical target in the amnion for treatment of pre- and post-term labor.

2021-07-15 | GSE166454 | GEO

C/EBPδ drives key endocrine signals in human fetal membranes at parturition [RNA-seq]

2021-07-15 | GSE166453 | GEO

Global gene expression profile of primary human leukemic blasts

Project description:The goal of this study is to define the global gene expression profile of primary leukemic blasts from patients with different forms of myeloid leukemia and different FAB subtypes. Here we report the global gene expression profile of 2 patients with AML FAB M5, 2 patients with AML FAB M7, 3 patients with Down syndrome AML FAB M7 and 3 patients with Down syndrome transient leukemia.

2009-12-29 | GSE19681 | GEO

Transcriptome of primary acute myeloid leukemia (AML) cells treated with AICAr

Project description:Ribonucleoside AICAr, a precursor in purine synthesis and a known activator of AMPK, was shown to induce monocytic differentiation in AML cell lines by inducing pyrimidine depletion followed by activation of ATR/Chk1 pathway and cell cycle arrest. Here we report transcriptional changes induced by AICAr in the primary AML sample (FAB-M2, FLT3 negative, NPM1 negative) in which AICAr induced differentiation and accumulation of macrophage cells in vitro. RNA-seq transcriptome analysis of primary AML cells isolated from the bone marrow of a patient with de novo FAB-M2 AML. Mononuclear cells were isolated from the bone marrow sample by density gradient separation and grown in RPMI supplemented with 10% FBS, 2 mM L-glutamine, 50 U/ml penicillin, 50 μg/ml streptomycin and 50 ng/ml IL-3, IL-6, SCF and FLT3L. Cells were treated with AICAr (0.4 mM) for 24 h. Experiment was performed in biological triplicates and total RNA was isolated for transcriptome analysis using Illumina high throughput sequencing.

2020-11-01 | E-MTAB-9209 | biostudies-arrayexpress

C/EBPδ drives key endocrine signals in human fetal membranes at parturition

Project description:C/EBPδ drives key endocrine signals in human fetal membranes at parturition

| PRJNA700435 | ENA

Hypoxia limits the tumor-suppressive effects of C/EBPδ in pancreatic cancer

Project description:Hypoxia limits the tumor-suppressive effects of C/EBPδ in pancreatic cancer

| PRJNA938416 | ENA

CDKN1B encoding the cyclin-dependent kinase inhibitor 1B (p27) is located in the minimally deleted region of 12p abnormalities in myeloid malignancies and its low expression is a favorable prognostic marker in acute myeloid leukemia

Project description:Alterations of the short arm of chromosome 12 (12p) occur in various hematological malignancies and ETV6 and CDKN1B, which are located on 12p, have been implicated as leukemogenic genes of interest. Design and Methods: We selected 7 patients with myeloid malignancies and small 12p deletions by FISH encompassing only the region centromeric of ETV6 and further evaluated them by SNP microarrays. Results: The minimal deleted region (MDR) contained nine genes only. These genes were subsequently analyzed by microarray expression profiling in an independent cohort of 781 cases mostly with different hematological malignancies or without any hematological malignancy: CREBL2, MANSC1, and CDKN1B were expressed in >25% of cases, while the other 6 genes were expressed in a minority of cases only. As CDKN1B is a cell cycle regulator and functions as a tumor suppressor gene, this gene was selected for further expression studies in 286 AML patients. In cases with low CDKN1B expression (expression level <1,160; 1st quartile), RUNX1-RUNX1T1 (11/83; 13.3%; vs. 5/203; 2.5%; p=0.001), PML-RARA rearrangements (11/83; 13.3%; vs. 4/203; 2.0%; p<0.001), 11q23/MLL rearrangements (6/83; 7.2%; vs. 4/203; 2.0%; p=0.038), and FLT3-TKD mutations (7/63; 11.1% vs. 6/167; 3.6%; p=0.047) were more frequently observed than in patients with intermediate/high expression (2nd-4th quartiles). Low CDKN1B expressers had longer median OS and EFS (not reached vs. 14.9 months; p=0.005 and 31.0 vs. 9.7 months; p=0.013, respectively) than intermediate/high expressers. Conclusions: CDKN1B is an interesting candidate gene as a potential biomarker for acute myeloid leukemia prognostication. Affymetrix SNP arrays were performed according to the manufacturer's directions using DNA extracted from mononuclear cells after Ficoll density centrifugation from bone marrow or peripheral blood samples.

2011-12-16 | E-GEOD-27832 | biostudies-arrayexpress

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