Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

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. 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE240864 | GEO | 2024/05/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

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

| PRJNA1005605 | ENA

Combination therapy with low dose ruxolitinib and cyclosporine in murine immune bone marrow failure

Project description:Combination therapy with low dose ruxolitinib and cyclosporine in murine immune bone marrow failure

| PRJNA1005598 | ENA

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

Identification of potential of new therapeutic approaches for JAK2 V617F mutant patients

Project description:n patients with PMF, excessive secretion of inflammatory cytokines results in fibrotic changes in bone marrow and diminishes the quality of life of the affected patients due to systemic symptoms long-term ruxolitinib therapy may reverse or markedly delay BM fibrosis progression in advanced MF suggests kavasincha 2018

2023-05-18 | PXD027250 | Pride

Granulocytic myeloid-derived suppressor cells to prevent and treat murine immune-mediated bone marrow failure

Project description:Background and methods: Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells which originate in the bone marrow (BM) and have immunoregulatory functions. MDSCs have been implicated in the pathogenesis of several autoimmune diseases but not in immune aplastic anemia (AA). We examined the roles of granulocytic-MDSCs (G-MDSCs) in murine models of human AA and bone marrow failure (BMF). To perform Totalseq, bone marrow mononuclear cells were FACS sorted to obtain alive cells based on FSC and SSC from five bone marrow failure control mice and five G-MDSC-treated mice, mRNA profiles of single cells were generated and sequenced on an Illumina Novaseq System. Results: As both prophylaxis and therapy, BM-derived G-MDSCs improved pancytopenia and BM cellularity and decreased BM T cell infiltration in major histocompatibility (MHC)-matched CB10 BMF mice. Single cell RNA sequencing demonstrated that G-MDSCs downregulated cell cycle related pathways in BM infiltrated T cells, consistent with suppression of T cell proliferation by G-MDSCs. Conclusion: Our results demonstrate that BM-derived G-MDSCs improved pancytopenia and BM cellularity and decreased BM T cell infiltration in major histocompatibility (MHC)-matched CB10 BMF mice, but not in MHC-mismatched CByB6F1 BMF model. Therapeutic efficacy of G-MDSCs are immune context-dependent. Bone marrow mononuclear cells were FACS sorted to obtain alive cells based on FSC and SSC from five bone marrow failure control mice and five G-MDSC-treated mice.

2022-07-27 | GSE193421 | GEO

Toxicicty of ruxolitinib in normal mice

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. 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.

2024-05-08 | GSE240866 | GEO

Gene expression profiling of low-dose irradiated human BM-MSCs

Project description:In bone marrow (BM), there are two different types of stem/progenitor cells. With respect to hematopoiesis, hematopoietic stem/progenitor cells (HPCs) produce mature blood cells and mesenchymal stromal/stem cells (MSCs) support this. The influence of exposure to low-dose radiation on human HPCs has been investigated, and generation of both immature and mature hematopoietic cells from human HPCs is compromised. On the other hand, the influence of exposure to low-dose radiation on MSCs is not known. This gene expression profiling was created for investigation how low-dose irradiation affects BM-MSCs genomically.

2017-09-01 | GSE97368 | GEO

Oxidative stress in myelodysplastic syndromes

Project description:Control of oxidative stress in the bone marrow (BM) is key for maintaining the balance between self-renewal, proliferation, and differentiation of hematopoietic cells. Breakdown of this regulation can lead to diseases characterized by BM failure such as the myelodysplastic syndromes (MDS). To better understand the role of oxidative stress in MDS development, we compared protein carbonylation as an oxidative stress marker in BM of patients with MDS and control subjects, and also patients with MDS under treatment with the iron chelator deferasirox.

2019-10-30 | PXD013609 | Pride

Gene expression profile of HSC/Ps and mature myeloid cells in MDS mutant clone

Project description:MDS are characterized by bone marrow (BM) failure due to ineffective hematopoiesis. However, the underlying mechanisms of ineffective hematopoiesis, in which clonal expansion coexists with accelerated cell death, remain to be elucidated. Recently, we detected CBL exon 8/9 deletion mutation (CBLΔE8/9) in several MDS patients with RUNX1 mutations. The CBLΔE8/9/RUNX1S291fs mice (CR-mice) developed a variety of MDS phenotypes, such as pancytopenia, dysplasia, and ineffective hematopoiesis in BM. RNA-Seq of HSC/progenitor (HSC/P) and mutant mature myeloid BM cells revealed that gene signature induced in the CR-mice is similar to that in MDS patients with BM failure. Especially, innate immune-related genes were significantly dysregulated.

2021-08-16 | GSE151694 | GEO

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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