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• W4313236823 abstract "Abstract Background It is known that the microenvironmental cytokine interferon gamma (IFN‐γ) provides a survival advantage for chronic lymphocytic leukemia (CLL) cells. However, the mechanisms involved in this effect have not been properly investigated. Methods Herein, we conducted a comprehensive screening of the effects of IFN‐γ on signaling pathways and gene expression profiles in CLL cells by using western blotting, real‐time quantitative reverse transcription (RT‐qPCR) and high‐throughput RNA sequencing (RNA‐seq). Results We found that IFN‐γ not only activated the pro‐survival signal transducer and activator of transcription 3 (STAT3), but also activated the protein kinase B and extracellular signal‐regulated kinase signaling pathways. RNA‐seq analysis showed that IFN‐γ stimulation changed the expression profiles of more than 500 genes, with 391 being up‐regulated and 123 down‐regulated. These genes are involved in numerous biological processes, including anti‐apoptosis, cell migration, and proliferation. IFN‐γ significantly up‐regulated the expression of CD38 , BCL6 , CXCL9 , BCL2A1 , SCOS3 , IL‐10 , HGF , EGFR , THBS‐1 , FN1 , and MUC1 , which encode proteins potentially associated with disease progression, worse prognosis or poor response to treatment. Blocking janus kinases1/2 (JAK1/2) or STAT3 signal by specific inhibitors affected the expression of most genes, suggesting a pivotal role of the JAK1/2‐STAT3 pathway in IFN‐γ pro‐survival effects in CLL. Conclusions Our data demonstrate that IFN‐γ regulates a complex pro‐survival signal network in CLL through JAK1/2‐STAT3, which provides a rational explanation for IFN‐γ promoting CLL cells survival and drug resistance." @default.
• W4313236823 created "2023-01-06" @default.
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• W4313236823 date "2023-01-12" @default.
• W4313236823 modified "2023-10-14" @default.
• W4313236823 title "Interferon gamma regulates a complex pro‐survival signal network in chronic lymphocytic leukemia" @default.
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• W4313236823 doi "https://doi.org/10.1111/ejh.13921" @default.
• W4313236823 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36576398" @default.
• W4313236823 hasPublicationYear "2023" @default.
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