Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Toxicicty of ruxolitinib in normal mice

ABSTRACT: Background and methods: Ruxolitinib (RUX), a Jak1/2 inhibitor, has been reported to attenuate murine bone marrow failure recently. Its potential toxocicty of anemia and thrombocytopenia in human remains a concern. We tested the toxicity of ruxolitinib on hematopoiesis in normal mice by feeding the mice with RUX chow for 3 months. Bone marrow Lin-CD117+ cells were sorted from treated or untreated mice. RNA-Seq and analysis was performed using SMART-Seq mRNA LP Kit (Takara) and the Illumina Novaseq6000, according to the Institute's protocols. Results: Ruxolitinib reduced RBC and lymphocytes, but did not affect NEU and PLT in normal mice. RNA sequencing demonstrated that HSPCs from RUX-treated and untreated mice had overlapped transcriptome distribution in multiple dimentional scalling plot, indicating overall similarity at molecular level. Conclusion: Our results demonstrate that ruxolitinib has minimal toxicity on hematopoiesis in normal mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE240866 | GEO | 2024/05/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Low dose ruxolitinib plus cyclosporine to treat murine immune-mediated bone marrow failure

Project description:Background and methods: Ruxolitinib (RUX), a Jak1/2 inhibitor, has been reported to attenuate murine bone marrow failure recently. Its potential toxocicty of anemia and thrombocytopenia in human remains a concern. To minimize its potential toxoxicity, we tested therapeutic effectsof low dose ruxolitinib plus cyclosporine in murine model of immune-mediated bone marrow failure. Bone marrow CD8 and CD4 T cells were sorted from treated or untreated bone marrow failure mice. RNA-Seq and analysis was performed using SMART-Seq mRNA LP Kit (Takara) and the Illumina Novaseq6000, according to the Institute's protocols. Results: low dose of ruxolitinib plus cyclosporine improved pancytopenia and BM cellularity and decreased BM T cell infiltration in bone marrow failure mice. RNA sequencing demonstrated that low dose of ruxolitinib plus cyclosporine suppressed immune-related pathways in bone marrow infiltrated CD8 T cells and MHC-II expression in CD4 T cells compared with untreated mice. Conclusion: Our results demonstrate that low dose of ruxolitinib plus cyclosporine remains the efficacy in attenuation of disease and extending survival of immune-mediated bone marrow failure mice.

2024-05-08 | GSE240864 | GEO

Efficacy of JAK 1/2 inhibition in murine immune bone marrow failure

Project description:Background and methods: Ruxolitinib (RUX) is a Jak inhibitor that is used in the treatment of intermediate or high risk myelofibrosis and resistant forms of polycythemia vera and graft-vs-host disease due to its efficacy of reducing inflammatory cytokines and markers of inflammation. We tested its potential therapeutic effects in murine models of immune-mediated bone marrow failure. RNA-Seq and analysis was performed using NEBNext Ultra™ II RNA Library Prep Kit for Illumina and Illumina Novaseq6000, according to the Institute's protocols. Results: As both prophylaxis and therapy, Ruxolitinib improved pancytopenia and BM cellularity and decreased BM T cell infiltration in bone marrow failure mice. RNA sequencing demonstrated that Ruxolitinib suppressed expression of inflammtory genes in bone marrow infiltrated CD8 T cells compared with untreated mice. Conclusion: Our results demonstrate that Ruxolitinib is highly effective in attenuation of disease and extending survival of immune-mediated bone marrow failure mice.

2023-01-29 | GSE196645 | GEO

TBCRC 039: A phase II study of preoperative ruxolitinib with or without paclitaxel for triple-negative inflammatory breast cancer

Project description:We conducted a randomized phase II study with nested window-of-opportunity in patients with TN-IBC. Patients were randomized to receive a 7-day run-in of ruxolitinib (RUX) alone or ruxolitinib plus paclitaxel (RUX+PAC) in a 1:2 ratio, followed by 12 weeks of neoadjuvant paclitaxel alone or in combination with ruxolitinib in a 1:2 ratio. All patients subsequently received 4 cycles of doxorubicin plus cyclophosphamide, followed by modified radical mastectomy. Patients provided tumor tissue from research biopsies performed at baseline (pre-run-in) and after the completion of run-in therapy. Tumor tissue was evaluated for phosphorylated STAT3 (pSTAT3) using immunohistochemistry (IHC) and immunofluorescence, and a subset of cases were also analyze by RNA-seq. The primary objective was to evaluate the percent of patients whose tumors were pSTAT3-positive at baseline, and which subsequently became pSTAT3-negative after run-in therapy. Secondary endpoints included pathologic complete response (pCR), residual tumor burden (RCB) and event-free survival (EFS) from the date of surgery. There were 23 patients enrolled, 11 in RUX and 12 in RUX+PAC combination. The most common adverse events were fatigue and nausea. Two patients achieved pCR and 21 completed pre-operative therapy. We detected a decrease in pSTAT3 and IL6/JAK/STAT3 signaling pathways in post-run-in biopsies of RUX-treated samples, but this did not correlate with pCR, while RUX+PAC upregulated IL6/JAK/STAT3 signaling. Both treatments decreased GZM+ T cells implying immune suppression, which might have contributed to lack of efficacy.

2024-02-07 | GSE232764 | GEO

Effect of genom-wide depletion on gene expression during treatment with the JAK2 inhibitor Ruxolitinib of JAK2 mutated HEL erythroleukemia cells [CRISPR]

Project description:In order to confirm the functional dependency on KDM4C under treatment conditions with the JAK-inhibitor ruxolitinib (RUX), we applied a genome-wide CRISPR-Cas9 screen in the human JAK2-mutated cell line HEL by CRISPR/Cas9.

2022-05-18 | GSE203059 | GEO

Expression data from WT and ISG15 KO HaCaT cells stimulated with interferon-a and treated with combination treatment of Ruxolitinib, TGFb and Doxycycline

Project description:Analysis of gene expression in WT and ISG15 KO HaCaT cells, stimulated with IFNa and treated with ruxolitinib (RUX), transforming growth factor beta (TGFb) and doxycycline (DOXY) to investigate the effects of treatments on transcriptional response in the cells.

2022-03-17 | GSE186391 | GEO

Expression data from hiPSC derived WT and ISG15 KO endothelial cells stimulated with interferon-a and treated with itaconic acid, dimethyl itaconate, 4-octyl itaconate and ruxolitinib

Project description:Analysis of gene expression in WT and ISG15 KO endothelial cells, stimulated with IFNa and treated with Itaconic acid (IA), Dimethyl itaconate (DI), 4-octyl itaconate (4OI) and ruxolitinib (RUX) to investigate the effects of treatments on transcriptional response in the cells.

2022-06-07 | GSE168747 | GEO

Label-free quantitative proteomics analysis of bone marrow cells of MK-LCM WT versus KO mice

Project description:High ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of hematopoietic stem cells (HSC) and are responsible for platelet formation. Using a mouse knockout model with normal megakaryocyte numbers but essentially devoid of LCM (MK-LCM KO), we demonstrated a pronounced increase in bone marrow HSC concurrent with endogenous mobilization and extramedullary hematopoiesis. When HSC isolated from a MK-LCM KO microenvironment were transplanted in lethally irradiated mice, the absence of LCM increased HSC in BM, blood and spleen. Severe thrombocytopenia was observed in animals with diminished LCM, although there was no change in megakaryocyte ploidy distribution. In contrast, WT HSC-generated LCM regulated a normal HSC pool and prevented thrombocytopenia. The present label-free quantitative LC-MSMS data was used to determine proteins that are differentially expressed in bone marrow cells of MK-LCM WT versus MK-LCM KO mice.

2023-05-10 | PXD040423 | Pride

Immune profiling in mice treated with BCL2 or JAK1/2 inhibitors

Project description:This study examined the impact of venetoclax or ruxolitinib on the immune profile of the bone marrow in treated mice showing venetoclax reduced expression of MHC-II and IFNg associated genes while ruxolitinib upregulated MHC-II and downregulated IFNg associated genes.

2021-10-13 | GSE181060 | GEO

Ints11 is essential for normal function of hematopoietic stem/progenitor cells [RNA-seq]

Project description:To investigate the role of INTS11 in normal hematopoiesis, Ints11 conditional KO mouse model was generated. We purified the Lin-cKit+ cells from bone marrow of WT and Ints11 KO mice and studied the differentially expressed genes due to the Ints11 loss.

2021-09-22 | GSE159403 | GEO

Bromodomain member BRD4 is required for hematopoietic stem cell functions (RNA-Seq)

Project description:To investigate the role of BRD4 in normal hematopoiesis, Brd4 conditional KO mouse model was generated. We purified the Lin-cKit+ cells from bone marrow of WT and Brd4 KO mice and performed the RNA-seq to study the molecular changes in each cell population.

2023-08-20 | GSE189834 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data