Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA259198 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Chromosome 5q deletions (del(5q)) are common in high-risk (HR) Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML); however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q) HR-MDS/AML and miR-146a-/- hematopoietic stem/progenitor cells (HSPC) results in TRAF6/NF-κΒ activation. Increased survival and proliferation of HSPC from miR-146alow HR-MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62), expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-κB-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-κB signaling, as disrupting the p62-TRAF6 signaling complex results in cell cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q) HR-MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-κB to sustain TRAF6/NF-κB signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML.
2014-08-23 | GSE60649 | GEO
Project description:Chromosome 5q deletions (del(5q)) are common in high-risk (HR) Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML); however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q) HR-MDS/AML and miR-146a-/- hematopoietic stem/progenitor cells (HSPC) results in TRAF6/NF-M-NM-:M-NM-^R activation. Increased survival and proliferation of HSPC from miR-146alow HR-MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62), expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-M-NM-:B-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-M-NM-:B signaling, as disrupting the p62-TRAF6 signaling complex results in cell cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q) HR-MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-M-NM-:B to sustain TRAF6/NF-M-NM-:B signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML. Four del(5q) MDS/AML patients with low miR-146a expression (5284, 8839, 8285, 4233) and 5 with high miR-146a expression (7957, 5534, 4688, 4982, 8412) were selected for microarray assay. RNA was reverse transcribed and labeled, and hybridized onto the GeneChip Human Gene 1.0 ST Array. A total of nine samples were included, and two groups are assigned based on miR-146a expression. Comparison comprises mRNA expression profile of low miR-146a group v.s. high miR-146a group.
2014-08-23 | E-GEOD-60649 | biostudies-arrayexpress
Project description:Genetic abnormalities including copy number variants (CNVs, such as gains and losses), and gene mutations are important for diagnosis and treatment of myeloid malignances. In a routine clinical setting, somatic gene mutations are detected by targeted next generation sequencing (NGS), but CNVs are commonly detected by conventional chromosome analysis and fluorescence in situ hybridization (FISH). The aim of this proof-of-principle study was to investigate the feasibility of using a targeted NGS assay to simultaneously detect not only somatic mutations, but also CNVs. Here, we sequenced 406 consecutive patients with myeloid malignancies and performed a head-to-head comparison with the results from conventional clinical assays including conventional chromosome analysis and myeloid FISH to detect CNVs. The targeted NGS assay revealed all 120 CNVs detected by myeloid FISH panel including monosomy 5/5q deletions, monosomy 7/7q deletions, trisomy 8, and 20q deletions. Furthermore, the targeted NGS assay also detected 605 CNVs outsides targeted regions of the myeloid FISH panel, which were revealed by conventional cytogenetic testing. The targeted NGS assay achieved 100% concordance with the myeloid FISH for detection of these common myeloid CNVs, with a high clinical sensitivity (> 99%) and specificity (>99%). The lower limit of detection by the myeloid FISH and the targeted NGS assay was similar and was generally 5% variant allele fraction for DNA. This proof-of-principle study demonstrated that the targeted NGS assay can simultaneously detect both common myeloid CNVs and somatic mutations, which can provide more comprehensive genetic profiling for patients with myeloid malignancies using a single assay.
2021-01-29 | GSE165733 | GEO
Project description:MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.
2018-11-28 | PXD011537 | Pride
Project description:RSK1 is an exploitable dependency in myeloid malignancies.
| PRJNA951429 | ENA
Project description:This project aimed to identify a specific target for chromosome 8p deletions. Using large-scale functional-genomic screening data of over 527 well-characterized cancer cell lines. We were able to identify the dependency of SLC25A28 (Mitoferrin-2, MFRN2), a mitochondrial iron transporter, in chromosome 8p deleted cancer cell lines. Interestingly, we found that SLC25A37 (Mitoferrin-1, MFRN1), the paralog of MFRN2, resides on chromosome 8p and is frequently deleted in liver cancer. We found a strong correlation between the cellular dependency on MFRN2 and the MFRN1 expression levels, possibly explaining why MFRN2 is a synthetic lethal target for 8p deletions. Our study discovered MFRN2 as a target for a therapeutic strategy in chromosome 8p deleted cancer specimens. Further, it revealed MFRN1 as a biomarker that predicts the response to MFRN2-directed therapy.
2024-06-03 | PXD044780 | Pride
Project description:RSK1 is an exploitable dependency in myeloid malignancies
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Project description:RSK1 is an exploitable dependency in myeloid malignancies
2024-11-14 | GSE229174 | GEO
Project description:RSK1 is an exploitable dependency in myeloid malignancies
2024-11-14 | GSE228759 | GEO
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2024-11-14 | GSE228758 | GEO