XPO1-dependency of DEK::NUP214 leukemia sensitizes against eltanexor
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1126303 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29481400_1.fastq.gz | Fastqsanger.gz | |||
| SRR29481400_2.fastq.gz | Fastqsanger.gz | |||
| SRR29481401_1.fastq.gz | Fastqsanger.gz | |||
| SRR29481401_2.fastq.gz | Fastqsanger.gz | |||
| SRR29481402_1.fastq.gz | Fastqsanger.gz |
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Project description:We aimed to investigate the role of XPO1 in this rare leukemia subtype. ChIP-sequencing was performed for XPO1 and NUP214 (as surrogate for DEK::NUP214 protein), and found co-occupancy of both proteins in putative DEK::NUP214 target genes.
2025-03-28 | GSE270396 | GEO
Project description:We aimed to investigate the role of XPO1 in this rare leukemia subtype. RNA-seq was performed in DEK::NUP214 expressing cell line in control and eltanexor-treated samples, an inhibitor of XPO1, to elucidate the genes and pathways involved in DEK::NUP214 AML
2025-03-28 | GSE270397 | GEO
Project description:Among most of leukemogenic fusion proteins the aberrant localization that the translocation partners are forced in when compared to their wt counterparts contributes to leukemogenesis most likely by a sequester of interaction partners. The aim was to disclose the role of localization of DEK/NUP214 and the related sequester of proteins interacting with DEK/NUP214 for the induction t(6;9)- AML. The pathways indispensable for the induction of the leukemogenic phenotype were worked out by comparing the interactome of the full-length fusion protein to that of biologiaclly-dead mutants.
2022-10-14 | PXD031885 | Pride
Project description:Acute Myeloid Leukemia (AML) represents a heterogeneous group of hematological malignancies. The t(6;9)(p23;q34) translocation, giving rise to the DEK::NUP214 fusion protein, is a rare mutation which produces a highly aggressive AML associated with extremely poor prognosis. Here, we utilise genome-wide chromatin accessibility to elucidate how a normal gene regulatory networks is disrupted by DEK::NUP214. We find that DEK::NUP214 AML forms a specific GRN related to that of mutant NPM1 AML, but also displays an elevated leukemic stem cell signature, suggesting both similar and unique therapeutic vulnerabilities.
2024-01-04 | GSE240268 | GEO
Project description:Acute Myeloid Leukemia (AML) represents a heterogeneous group of hematological malignancies. The t(6;9)(p23;q34) translocation, giving rise to the DEK::NUP214 fusion protein, is a rare mutation which produces a highly aggressive AML associated with extremely poor prognosis. Here, we utilise genome-wide chromatin accessibility to elucidate how a normal gene regulatory networks is disrupted by DEK::NUP214. We find that DEK::NUP214 AML forms a specific GRN related to that of mutant NPM1 AML, but also displays an elevated leukemic stem cell signature, suggesting both similar and unique therapeutic vulnerabilities.
2024-01-04 | GSE240267 | GEO
Project description:Introduction: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer, exhibiting rapid progression and is unresponsive to hormone therapy. Reliable prognostic assays and more effective treatments are critically required. However, the research of NEPC has been hampered by a lack of clinically relevant in vivo models. Recently, we successfully developed a first-in-field patient tissue-derived xenograft model of complete neuroendocrine transdifferentiation from prostate adenocarcinoma. By comparing gene expression profiles of the parental adenocarcinoma line (LTL331) and the NEPC subline (LTL331R), we identified DEK, a gene not previously reported in prostate cancer, as a potential biomarker and target for NEPC. Methods: DEK protein expression in patient tissue-derived xenograft models and clinical samples was assessed by immunohistochemistry. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis. Results: Elevated DEK protein expression was observed in all clinical NEPC cases, which is distinct from their benign counterparts (0%), hormonal naïve prostate cancer (2.45%) and castration resistant prostate cancer (29.55%). Increased DEK expression is an independent clinical risk factor and is associated with shorter disease free survival in hormonal naïve prostate cancer patients. Reduction of DEK expression in PC-3 cells led to a marked reduction in cell proliferation, cell migration and invasion. Conclusions: The results suggest that DEK may play an important role in the progression of prostate cancer, especially NEPC and provide a potential biomarker to aid risk stratification of prostate cancer and a novel therapeutic target for treating NEPC. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis.
2015-01-15 | E-GEOD-61214 | biostudies-arrayexpress
Project description:We find that the DEK oncoprotein preferentially binds close to the transcription start sites of highly and ubiquitously expressed genes. Sequencing of DNA precipitated by an antibofy against the DEK oncoprotein (ChIP-seq).
2014-09-26 | E-GEOD-60692 | biostudies-arrayexpress
Project description:This study aims to investigate the role and mechanism of DEK in asthmatic airway inflammation and in regulating PTEN-induced putative kinase 1 (PINK1)-Parkin mediated mitophagy, NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasome activation, and apoptosis. We found that recombinant DEK protein (rmDEK) promoted eosinophils recruitment, mitochondrial fragmentation, and outer membrane 20 (TOM20) and LC3 co-localization representing mitophagosomes in bronchoalveolar lavage fluid (BALF) in house dust mite (HDM) induced-asthma. rmDEK also reduced co-localization of mitochondrial fusion protein mitofusin1 (MFN1) and mitochondria, and the protein level of manganese superoxide dismutase (MnSOD), enhanced microtubule-associated protein1 light chain 3 (LC3) and voltage-dependent anion channels (VDAC) co-localization which also represent the mitophagosomes in airway epithelial cells, furthermore, increased dynamin-related protein 1 (DRP1) expression, PINK1-Parkin-mediated mitophagy, NLRP3 inflammasome activation, and apoptosis. In the DEK knockout mice, HDM induced asthmatic airway inflammation, MnSOD, PINK1-Parkin protein level, Parkin mediated mitophagy characterized by LC3 and Parkin co-localization in the airways, ROS generation, NLRP3 inflammation and apoptosis were fully reversed. Similar effects of rmDEK were also observed in the BEAS-2B cells, which were rescued by the autophagy inhibitor 3-MA. Moreover, DEK silencing diminished the Parkin, LC3, DRP1 translocation to mitochondria; as well as mitochondrial ROS; TOM20 and mitochondrial DNA mediated mitochondrial oxidative damage. ChIP-sequence analysis showed that DEK was enriched on the AAA domain-containing protein 3A (ATAD3A) promoter and could positively regulate ATAD3A expression. Additionally, ATAD3A was highly expressed in HDM-induced asthma models. Furthermore, ATAD3A interacted with DRP1, and knockdown of ATAD3A could down-regulate DRP1 and mitochondrial oxidative damage. Conclusively, DEK deficiency alleviates airway inflammation in asthma by down-regulating PINK1-Parkin mitophagy, NLRP3 inflammasome activation, and apoptosis. The mechanism may be through the DEK/ATAD3A/DRP1 signaling axis. Our findings may provide new potential therapeutic targets for asthma treatment.
2023-09-24 | GSE243532 | GEO
Project description:Gene expression profiling of U937 cells upon knockdown of the DEK oncogene by two different shRNAs (shDEK14 and shDEK17). The DEK oncogene was knocked down by shRNA to study the changes in gene expression.
2014-09-26 | E-GEOD-60732 | biostudies-arrayexpress
Project description:XPO1 gene encodes exportin 1 (XPO1) that controls the nuclear export of cargo proteins and RNAs. Almost 25% of primary mediastinal B-cell lymphomas (PMBL) and classical Hodgkin lymphomas (cHL) cases harboured a recurrent XPO1 point mutation (NM_003400, chr2:g61718472C>T) resulting in the E571K modification within the hydrophobic groove of the protein, the site of cargo proteins binding. We investigated the functional impact of XPO1E571K mutation using cell lines having various XPO1 status. We first confirmed that the mutation was present both within the XPO1 mRNA and the corresponding protein. In the U2940 cell line having a wild-type (wt) XPO1 gene, we introduced the E571K mutation using several CRISPR-Cas9 strategies. Using a barcoding method to trace the mutation, we observed that the mutation gave no advantage in vitro. Indeed, the effects of XPO1E571K mutation were hidden by the presence of the XPO1 wt allele. Strikingly, XPO1E571K mutation never occurred as homozygous or hemizygous in our patients��������� cohort. We further showed that XPO1E571K mutation modified selinexor binding to XPO1 and in turn, its sensitivity to this drug. We concluded that the balance between the wild-type and the mutated allele of XPO1 is a key element in defining XPO1 functions and oncogenic properties.
2020-10-01 | PXD016916 | Pride