Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA195933 | ENA |
REPOSITORIES: ENA
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Project description:Leukemia cells instruct their surrounding bone marrow microenvironment (BMM) rendering it hospitable to leukemia cell survival. Conversely, how cells of the BMM influence leukemia progression is less well understood. Pleckstrin homology domain family M member 1 (PLEKHM1) serves as a hub between fusion and secretion of intracellular vesicles. Here, we performed label-free quantitative proteomics to investigate the exosomal cargo released by BMM-derived mesenchymal stromal cells (MSC) lacking Plekhm1 compared to wild-type cells.
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Project description:This data set consists of pediatric acute lymphoblastic leukemia (ALL) primary bone marrow biopsies from the BC Children's Hospital BioBank, pediatric ALL cell lines, non-cancer bone marrow biopsies, and few ALL PDX. All files are DIA and searched by Spectronaut with a spectral library.
2023-01-05 | MSV000091012 | MassIVE
Project description:Intercellular communication within the bone marrow niche significantly influences leukemogenesis and the sensitivity of leukemic cells to therapy. However, the landscape of possible cell-cell interactions is still incomplete. Tunneling nanotubes (TNTs) are a novel mode of intercellular cross-talk. They are long, thin membranous conduits that enable the direct transfer of various cargo between cells. The present study found that TNTs are formed between leukemic and bone marrow stromal cells. Confocal three-dimensional reconstructions, correlative light-electron microscopy, and electron tomography provided evidence that TNTs transfer cellular vesicles between cells. The quantitative analysis demonstrated the stimulation of TNT-mediated vesicle transfer from stromal cells to leukemic cells by the stromal component. The vesicular cargo that was received from stroma cells conferred resistance to anti-leukemic treatment. Moreover, specific sets of proteins with a potential role in survival and the drug response were transferred within these vesicles. Altogether, we found that TNTs are involved in a novel and potent mechanism that participates in leukemia-stroma cross-talk and the stroma-mediated cytoprotection of leukemic cells. Our findings implicate TNT connections as a possible target for therapeutic interventions within the leukemia microenvironment to attenuate stroma-conferred protection.
2019-11-11 | PXD013504 | Pride
Project description:Intercellular communication within the bone marrow niche significantly influences leukemogenesis and the sensitivity of leukemic cells to therapy. However, the landscape of possible cell-cell interactions is still incomplete. Tunneling nanotubes (TNTs) are a novel mode of intercellular cross-talk. They are long, thin membranous conduits that enable the direct transfer of various cargo between cells. The present study found that TNTs are formed between leukemic and bone marrow stromal cells. Confocal three-dimensional reconstructions, correlative light-electron microscopy, and electron tomography provided evidence that TNTs transfer cellular vesicles between cells. The quantitative analysis demonstrated the stimulation of TNT-mediated vesicle transfer from stromal cells to leukemic cells by the stromal component. The vesicular cargo that was received from stroma cells conferred resistance to anti-leukemic treatment. Moreover, specific sets of proteins with a potential role in survival and the drug response were transferred within these vesicles. Altogether, we found that TNTs are involved in a novel and potent mechanism that participates in leukemia-stroma cross-talk and the stroma-mediated cytoprotection of leukemic cells. Our findings implicate TNT connections as a possible target for therapeutic interventions within the leukemia microenvironment to attenuate stroma-conferred protection.
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Project description:The natural history of multiple myeloma is characterized by its localization to the bone marrow and its interaction with bone marrow stromal cells. The bone marrow stromal cells provide growth and survival signals, thereby promoting the development of drug resistance. Here, we show that the interaction between bone marrow stromal cells and myeloma cells (using human cell lines) induces chromatin remodeling of cis-regulatory elements and is associated with changes in the expression of genes involved in the cell migration and cytokine signaling. The expression of genes involved in these stromal interactions are observed in extramedullary disease in patients with myeloma and provides the rationale for survival of myeloma cells outside of the bone marrow microenvironment. Expression of these stromal interaction genes is also observed in a subset of patients with newly diagnosed myeloma and are akin to the transcriptional program of extramedullary disease. The presence of such adverse stromal interactions in newly diagnosed myeloma is associated with accelerated disease dissemination, predicts the early development of therapeutic resistance, and is of independent prognostic significance. These stromal cell induced transcriptomic and epigenomic changes both predict long-term outcomes and identify therapeutic targets in the tumor microenvironment for the development of novel therapeutic approaches.
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Project description:LYN kinase is a tyrosine kinase, that regulates cellular homeostasis in a context specific manner. Our group could show, that its expression in the leukemic microenvironment of chronic lymphocytic leukemia contributes to disease progression (Nguyen PH et al.; Cancer Cell; 2016). To analyze the effect of LYN kinase on the leukemia supportive phenotype of the bone marrow stromal cell line HS-5, we generated single cell clones of LYN deficient cells. These cells were analyzed in a Multi-Omic approach, including quantitative, label-free proteomic analysis of the Secretome.
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Project description:Mouse Bone-marrow Stromal Cell Lines Genetic Expression Comparison
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Project description:We analysed the transcriptional signature of bone marrow Nestin+ mesenchymal stromal cells extracted from the bone marrow of mice engrafted with human AML cell lines and compared it to the one of untransplanted mice
2021-04-14 | GSE148625 | GEO
Project description:LYN kinase is a tyrosine kinase, that regulates cellular homeostasis in a context specific manner. Our group could show, that its expression in the leukemic microenvironment of chronic lymphocytic leukemia contributes to disease progression (Nguyen PH et al.; Cancer Cell; 2016). To analyze the effect of LYN kinase on the leukemia supportive phenotype of the bone marrow stromal cell line HS-5, we generated single cell clones of LYN deficient cells. These cells were analyzed in a Multi-Omic approach, including quantitative, label-free proteomic analysis of the Proteome / SILAC labelled analysis of the tyrosine phosphoproteome.
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