Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA299255 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2731551.fastq.gz | Fastqsanger.gz | |||
| SRR2731552.fastq.gz | Fastqsanger.gz | |||
| SRR2731553.fastq.gz | Fastqsanger.gz | |||
| SRR2731554.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Recurrent gain-of-function mutations in the transcription factor STAT5 have been detected in PTCL, an aggressive, heterogeneous disease, for which currently no targeted therapy exists. Here we investigated whether constitutive activation of STAT5 suffices to drive PTCL and whether inhibition of the JAK/STAT pathway offers a novel therapeutic opportunity in this disease. We found pronounced STAT5 expression and activity in patients from different PTCL subsets. To mimic high STAT5 activity we expressed a hyperactive STAT5A variant (termed vcS5) in the hematopoietic lineage in transgenic mice. vcS5-transgenic animals developed a lethal PTCL-like disease with full penetrance, characterized by massive expansion of CD8+ T-cells and destructive organ-infiltration. Adoptive transfer of vcS5-expressing CD8+ T-cell rapidly induced the disease in immunocompetent recipient mice. Neoplastic vcS5-T-cells displayed cytokine-hypersensitivity and showed activated, memory CD8+ T-lymphocyte characteristics. Histo-pathological analysis as well as mRNA expression profiles of vcS5 mice was closely correlated with distinct human lymphoma subtypes, including PTCL. Treatment of murine and human PTCL cell lines with the clinical JAK inhibitor Ruxolitinib or a selective STAT5 SH2 domain inhibitor induced cell death. Thus, our results demonstrate that enhanced STAT5 signaling drives PTCL development and suggest inhibition of the JAK/STAT5 pathway as a valuable therapeutic option for patients suffering from these aggressive lymphomas.
2017-10-18 | GSE74176 | GEO
Project description:Peripheral T-cell lymphomas (PTCL) are aggressive diseases with poor response to chemotherapy and dismal survival. Identification of effective strategies to target PTCL biology represents an urgent need. Here we report that PTCL are sensitive to transcription-targeting drugs, and, in particular, to THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7). The STAT-signaling pathway is highly vulnerable to THZ1 even in PTCL cells that carry the activating STAT3 mutation Y640F. In mutant cells, CDK7 inhibition decreases STAT3 chromatin binding and expression of highly transcribed target genes like MYC, PIM1, MCL1, CD30, IL2RA, CDC25A and IL4R. In surviving cells, THZ1 decreases the expression of STAT-regulated anti-apoptotic BH3 family members MCL1 and BCL-XL sensitizing PTCL cells to BH3 mimetic drugs. Accordingly, the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients.
2016-12-15 | GSE79955 | GEO
Project description:Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P=.01). High expression of cytotoxic genesignaturewithin the TBX21 subgroup also showed poor clinical outcome (P=.05). InAITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P=.004).
2015-06-01 | GSE58445 | GEO
Project description:Recurrent gain-of-function mutations in the transcription factor STAT5B, but not STAT5A, have been detected in mature T- and NK-cell neoplasms. No targeted therapy exists for these heterogeneous and often aggressive diseases. Also, the bystander or balancer role for STAT5A versus STAT5B is unclear. Given this and the shortage of high-fidelity models for peripheral T-cell lymphomas (PTCL), we investigated here whether graded expression of a gain-of-function STAT5A variant produces tumorous T-cell expansions. To mimic STAT5 activity we expressed a hyperactive STAT5A variant at low or high levels in the hematopoietic system of transgenic mice (termed cS5Alo and cS5Ahi). Only cS5Ahi-mice developed a lethal disease resembling human PTCL with full penetrance, characterized by massive expansion of CD8+ T-cells and by destructive organ-infiltration. Neoplastic cS5Ahi-T-cells were cytokine-hypersensitive, showed cytotoxic features, and revealed activated memory CD8+ T-lymphocyte characteristics. Histopathology analysis and mRNA expression profiles of cS5Ahi tumors revealed close correlation with distinct human PTCL subtypes, similar to the hSTAT5BN642H mouse model expressing the most frequent STAT5B mutation. We found pronounced STAT5 expression and activity in patient samples of different PTCL subsets. Clinical-grade JAK inhibitors or a selective STAT5 SH2 domain inhibitor induced cell death in murine and human PTCL cell lines and Ruxolitinib (JAK1/2) ameliorated the disease in cS5Ahi mice.
2020-02-24 | GSE124102 | GEO
Project description:Some infectious agents are associated with non-Hodgkin lymphoma development. Here we have used p53-deficient mice chronically injected with Streptococcus pneumoniae (Spn) with the aim to develop an animal model of infection-associated lymphomagenesis. We show that repeated stimulations with heat-killed Spn significantly enhanced the incidence of peripheral T-cell lymphoma (PTCL) in these mice. Phenotypic studies and gene expression profile analyses indicate that these PTCL arose from chronically stimulated natural killer T (NKT) cells, a T cell lineage that exhibits unique properties. Furthermore, lymphoma development was blocked when these PTCL were transferred to recipients lacking CD1d expression or treated with blocking CD1d mAbs, thus demonstrating that in vivo TCR/CD1d interactions are required for these PTCL survival. In conclusion, we have identified a new entity of peripheral T-cell lymphoma that originates from CD1d-restricted natural killer T (NKT) cells. Our results could refine the classification of PTCL and pave the way for the development of new immunotherapeutic approaches.
2016-03-04 | GSE63264 | GEO
Project description:Peripheral T-cell lymphoma unspecified (PTCL/U), the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, and dismal prognosis. We demonstrate that PTCL/U shows a gene expression profile clearly distinct from that of normal T-cells. Comparison with the profiles of purified T-cell subpopulations [CD4+, CD8+, resting (HLA-DR-), and activated (HLA-DR+)] reveals that PTCLs/U are most closely related to activated peripheral T-lymphocytes, either CD4+ or CD8+. Interestingly, the global gene expression profile cannot be surrogated by routine CD4/CD8 immunohistochemistry. When compared with normal T-cells, PTCLs/U display deregulation of functional programs often involved in tumorigenesis (e.g. apoptosis, proliferation, cell adhesion, and matrix remodeling). Products of deregulated genes can be detected in PTCLs/U by immunohistochemistry with an ectopic, paraphysiologic or stromal location. Among others, PTCLs/U aberrantly express PDGFRA, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRA and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone-deacetylase) are found. These results, which might be extended to other rarer PTCL categories, are provided with implications for tumor pathogenesis and clinical management. Experiment Overall Design: 40 cases of Peripheral T-cell lymphoma (PTCL) were analyzed, including 28 PTCL/unspecified, 6 angioimmunoblastic (AITL) and 6 anaplastic large cell lymphoma cases (ALCL). Frozen lymph-nodes collected at diagnosis (before therapy) were used. In addition, 20 samples of normal T-cells (5 CD4+, 5 CD8+, 5 HLA-DR+, and 5 HLA-DR-) collected from peripheral blood and tonsils of healthy donors were studied. The HG U133 2.0 plus microarray (Affymetrix) was adopted.
2008-06-14 | E-GEOD-6338 | biostudies-arrayexpress
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:Peripheral T-cell Lymphoma cases along with normal T-cells were subjected to gene expression profiling by means of a DASL array. The cases included both PTCL/NOS and Lennert Lymphoma.
2019-09-19 | GSE132550 | GEO
Project description:Mouse model of RHOA G17V mutation in Peripheral T-Cell Lymphoma
| PRJNA327428 | ENA
Project description:The molecular biology of the primary nodal EBV-positive variant of PTCL (PTCL-EBV) and its relationship with extranodal NK/T-cell lymphoma (ENKTL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) remains poorly understood. In this study, we assessed the relationship between the three diseases using gene and EBV miRNA expression profiling, and copy number aberration (CNA) analyses and attempted to characterize the degree of genomic instability (GI). This series is the oncoscan CNA data of 77 NKTL samples.
2021-11-27 | GSE160118 | GEO