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OSM is induced by STAT5-activating oncogenes in a kinase-dependent manner and acts on bone marrow stromal cells via STAT3 phosphorylation. a <t>32D</t> cells were transduced with various oncogenes and starved of cytokines and serum for twelve hours. Quantitative PCR revealed Osm upregulation in BCR::ABL1-, FLT3-ITD-, NPM1::ALK-, and JAK2 p.V617F-positive cells. Osm expression values were normalized to Gapdh and empty vector (MiG-empty) expression values. N ≥ 3 experiments; p values (compared with MiG-empty cells): *** p < 0.001; ** p < 0.01. The data are presented as the means ± SEMs. b 32D cells transduced with oncogenes were serum-starved plus inhibitor-treated as indicated for twelve hours. Osm expression values were normalized to Gapdh and MiG-empty vector expression values. P values (compared with MiG-empty cells): *** p < 0.001; ** p < 0.01. The data are presented as the means ± SEMs. c Flow cytometric analysis of OSMR surface levels in primary human stromal cells, primary AML blasts, and human myeloid leukemic cell lines. The mean fluorescence intensity (MFI) of the isotype control was subtracted from the OSMR MFI values. Each dot represents one measurement. The data are presented as the means ± SEMs. d Primary murine hematopoietic BM cells (HCs) did not express Osmr transcripts after 40 PCR cycles, whereas mesenchymal stromal cell (MSC) populations expressed Osmr . MSC = mesenchymal stromal cells, OB = osteoblasts, ND = not detected. Each dot represents one measurement. The data are presented as the means ± SEMs. e Flow cytometric analysis of pSTAT3 levels in primary human stromal cells and human myeloid leukemic cell lines after huOSM treatment (2.5 h, 10 ng/mL). The mean fluorescence intensity (MFI) of the isotype control was subtracted from the pSTAT3 antibody MFI values. Each dot represents one measurement. The data are presented as the means ± SEMs. f , g OSM ( f ) and OSMR ( g ) expression across hematological and solid neoplasms utilizing Expression Public 24Q2 and lineage subtype grouping on the DepMap portal ( https://depmap.org )
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OSM is induced by STAT5-activating oncogenes in a kinase-dependent manner and acts on bone marrow stromal cells via STAT3 phosphorylation. a 32D cells were transduced with various oncogenes and starved of cytokines and serum for twelve hours. Quantitative PCR revealed Osm upregulation in BCR::ABL1-, FLT3-ITD-, NPM1::ALK-, and JAK2 p.V617F-positive cells. Osm expression values were normalized to Gapdh and empty vector (MiG-empty) expression values. N ≥ 3 experiments; p values (compared with MiG-empty cells): *** p < 0.001; ** p < 0.01. The data are presented as the means ± SEMs. b 32D cells transduced with oncogenes were serum-starved plus inhibitor-treated as indicated for twelve hours. Osm expression values were normalized to Gapdh and MiG-empty vector expression values. P values (compared with MiG-empty cells): *** p < 0.001; ** p < 0.01. The data are presented as the means ± SEMs. c Flow cytometric analysis of OSMR surface levels in primary human stromal cells, primary AML blasts, and human myeloid leukemic cell lines. The mean fluorescence intensity (MFI) of the isotype control was subtracted from the OSMR MFI values. Each dot represents one measurement. The data are presented as the means ± SEMs. d Primary murine hematopoietic BM cells (HCs) did not express Osmr transcripts after 40 PCR cycles, whereas mesenchymal stromal cell (MSC) populations expressed Osmr . MSC = mesenchymal stromal cells, OB = osteoblasts, ND = not detected. Each dot represents one measurement. The data are presented as the means ± SEMs. e Flow cytometric analysis of pSTAT3 levels in primary human stromal cells and human myeloid leukemic cell lines after huOSM treatment (2.5 h, 10 ng/mL). The mean fluorescence intensity (MFI) of the isotype control was subtracted from the pSTAT3 antibody MFI values. Each dot represents one measurement. The data are presented as the means ± SEMs. f , g OSM ( f ) and OSMR ( g ) expression across hematological and solid neoplasms utilizing Expression Public 24Q2 and lineage subtype grouping on the DepMap portal ( https://depmap.org )

Journal: Signal Transduction and Targeted Therapy

Article Title: Oncostatin M induced by STAT5-activating oncogenes promotes disease progression in hematologic malignancies

doi: 10.1038/s41392-025-02491-6

Figure Lengend Snippet: OSM is induced by STAT5-activating oncogenes in a kinase-dependent manner and acts on bone marrow stromal cells via STAT3 phosphorylation. a 32D cells were transduced with various oncogenes and starved of cytokines and serum for twelve hours. Quantitative PCR revealed Osm upregulation in BCR::ABL1-, FLT3-ITD-, NPM1::ALK-, and JAK2 p.V617F-positive cells. Osm expression values were normalized to Gapdh and empty vector (MiG-empty) expression values. N ≥ 3 experiments; p values (compared with MiG-empty cells): *** p < 0.001; ** p < 0.01. The data are presented as the means ± SEMs. b 32D cells transduced with oncogenes were serum-starved plus inhibitor-treated as indicated for twelve hours. Osm expression values were normalized to Gapdh and MiG-empty vector expression values. P values (compared with MiG-empty cells): *** p < 0.001; ** p < 0.01. The data are presented as the means ± SEMs. c Flow cytometric analysis of OSMR surface levels in primary human stromal cells, primary AML blasts, and human myeloid leukemic cell lines. The mean fluorescence intensity (MFI) of the isotype control was subtracted from the OSMR MFI values. Each dot represents one measurement. The data are presented as the means ± SEMs. d Primary murine hematopoietic BM cells (HCs) did not express Osmr transcripts after 40 PCR cycles, whereas mesenchymal stromal cell (MSC) populations expressed Osmr . MSC = mesenchymal stromal cells, OB = osteoblasts, ND = not detected. Each dot represents one measurement. The data are presented as the means ± SEMs. e Flow cytometric analysis of pSTAT3 levels in primary human stromal cells and human myeloid leukemic cell lines after huOSM treatment (2.5 h, 10 ng/mL). The mean fluorescence intensity (MFI) of the isotype control was subtracted from the pSTAT3 antibody MFI values. Each dot represents one measurement. The data are presented as the means ± SEMs. f , g OSM ( f ) and OSMR ( g ) expression across hematological and solid neoplasms utilizing Expression Public 24Q2 and lineage subtype grouping on the DepMap portal ( https://depmap.org )

Article Snippet: 32D, NIH/3T3 and OP9 cells were obtained from the German Resource Centre for Biological Material (DSMZ).

Techniques: Phospho-proteomics, Transduction, Real-time Polymerase Chain Reaction, Expressing, Plasmid Preparation, Fluorescence, Control