Matches in SemOpenAlex for { <https://semopenalex.org/work/W1992720072> ?p ?o ?g. }
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- W1992720072 abstract "B-cell lymphoma is the most common immune system malignancy. TCL1 transgenic mice (TCL1-tg), in which TCL1 is ectopically expressed in mature lymphocytes, develop multiple B- and T-cell leukemia and lymphoma subtypes, supporting an oncogenic role for TCL1 that probably involves AKT and MAPK-ERK signaling pathway augmentation. Additional, largely unknown genetic and epigenetic alterations cooperate with TCL1 during lymphoma progression. We examined DNA methylation patterns in TCL1-tg B-cell tumors to discover tumor-associated epigenetic changes, and identified hypermethylation of sprouty2 (Spry2). Sprouty proteins are context-dependent negative or positive regulators of MAPK-ERK pathway signaling, but their role(s) in B-cell physiology or pathology are unknown. Here we show that repression of Spry2 expression in TCL1-tg mouse and human B-cell lymphomas and cell lines is associated with dense DNA hypermethylation and was reversed by inhibition of DNA methylation. Spry2 expression was induced in normal splenic B cells by CD40/B-cell receptor costimulation and regulated a negative feedback loop that repressed MAPK-ERK signaling and decreased B-cell viability. Conversely, loss of Spry2 function hyperactivated MAPK-ERK signaling and caused increased B-cell proliferation. Combined, these results implicate epigenetic silencing of Spry2 expression in B lymphoma progression and suggest it as a companion lesion to ectopic TCL1 expression in enhancing MAPK-ERK pathway signaling." @default.
- W1992720072 created "2016-06-24" @default.
- W1992720072 creator A5011370023 @default.
- W1992720072 creator A5031330950 @default.
- W1992720072 creator A5033298543 @default.
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- W1992720072 creator A5045356809 @default.
- W1992720072 creator A5082699765 @default.
- W1992720072 creator A5090085505 @default.
- W1992720072 date "2002-06-01" @default.
- W1992720072 modified "2023-10-12" @default.
- W1992720072 title "DNA Methylation Profiling: A New Tool for Evaluating Hematologic Malignancies" @default.
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