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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE203059 | GEO | 2022/05/18

REPOSITORIES: GEO

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Effect of depletion of KDM4C on gene expression of JAK2-mutated HEL erythroleukemia cells [RNA-seq]

Project description:To investigate the function of KDM4C in progression of leukemia, we established HEL-Cas9 cell lines in which the target gene has been knocked out by CRISPR/Cas9. We then performed transcriptome analysis using data obtained from RNA-seq of control or KDM4C depletd cells.

2022-05-18 | GSE203060 | 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

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

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

| PRJNA838373 | ENA

Effect of depletion of KDM4C on gene expression of JAK2-mutated HEL erythroleukemia cells [RNA-seq]

Project description:Effect of depletion of KDM4C on gene expression of JAK2-mutated HEL erythroleukemia cells [RNA-seq]

| PRJNA838374 | ENA

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

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

Genome-wide occupancy of LSD1 in HEL human erythroleukemia cell line.

Project description:We examined the genome-wide distribution of LSD1 bound regions in HEL cells bya ChIP-seq analysis. We found that GATA family transcription factors co-operate with LSD1 to regulate metabolic genes. We also found that LSD1 binds to and represses CEBPA gene enhancer, resulting in the suppression of myeloid cell properties.

2021-05-04 | GSE145401 | 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

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

PolyA RNA sequencing of HEL human erythroleukemia cell line under LSD1 inhibition

Project description:To understand the role of LSD1 in transcriptional regulation, RNA-seq analyses of LSD1-inhibited HEL cells were carried out. Cells were collected after the introduction of lentiviral LSD1 shRNA or the treatment with a specific LSD1 inhibitor, S2101. We found that LSD1 inhibition led to decreased expression of genes involved in various metabolic pathways.

2021-05-04 | GSE145397 | GEO

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