NDLI: Expression of sprouty2 inhibits B-cell proliferation and is epigenetically silenced in mouse and human B-cell lymphomas

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Expression of sprouty2 inhibits B-cell proliferation and is epigenetically silenced in mouse and human B-cell lymphomas

Content Provider	Scilit
Author	Frank, Matthew J. Dawson, David W. Bensinger, Steven J. Hong, Jason S. Knosp, Wendy M. Xu, Lizhong Balatoni, Cynthia E. Allen, Eric L. Shen, Rhine R. Bar-Sagi, Dafna Martin, Gail R. Teitell, Michael A.
Copyright Year	2009
Description	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.
Related Links	http://www.bloodjournal.org/content/113/11/2478.full.pdf
Ending Page	2487
Page Count	10
Starting Page	2478
DOI	10.1182/blood-2008-05-156943
Journal	Blood
Issue Number	11
Volume Number	113
Language	English
Publisher	American Society of Hematology
Publisher Date	2009-03-12
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Tcl1 Cell Lymphomas Mapk Erk Epigenetically Silenced Cell Proliferation Dna Methylation Journal: Blood (Vol- 117, Issue- 11)
Content Type	Text
Resource Type	Article

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