Sprouty 2: a novel attenuator of B-cell receptor and MAPK-Erk signaling in CLL.

Blood
Ashima ShuklaShantaram S Joshi

Abstract

Clinical heterogeneity is a major barrier to effective treatment of chronic lymphocytic leukemia (CLL). Emerging evidence suggests that constitutive activation of various signaling pathways like mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-Erk) signaling plays a role in the heterogeneous clinical outcome of CLL patients. In this study, we have investigated the role of Sprouty (SPRY)2 as a negative regulator of receptor and nonreceptor tyrosine kinase signaling in the pathogenesis of CLL. We show that SPRY2 expression is significantly decreased in CLL cells, particularly from poor-prognosis patients compared with those from good-prognosis patients. Overexpression of SPRY2 in CLL cells from poor-prognosis patients increased their apoptosis. Conversely, downregulation of SPRY2 in CLL cells from good-prognosis patients resulted in increased proliferation. Furthermore, CLL cells with low SPRY2 expression grew more rapidly in a xenograft model of CLL. Strikingly, B-cell-specific transgenic overexpression of spry2 in mice led to a decrease in the frequency of B1 cells, the precursors of CLL cells in rodents. Mechanistically, we show that SPRY2 attenuates the B-cell receptor (BCR) and MAPK-Erk signaling ...Continue Reading

References

Oct 29, 2002·Nature Cell Biology·Hiroshi HanafusaEisuke Nishida
Jun 28, 2003·Journal of Cell Science·Graeme R GuyChee Wai Fong
Feb 16, 2005·The Journal of Clinical Investigation·Bradley T MessmerNicholas Chiorazzi
Feb 25, 2005·The New England Journal of Medicine·Nicholas ChiorazziManlio Ferrarini
Dec 13, 2005·Trends in Cell Biology·Jacqueline M MasonJonathan D Licht
Sep 5, 2006·Developmental Cell·Amélie CalmontKenneth S Zaret
Mar 21, 2007·Genes & Development·Alice T ShawTyler Jacks
Aug 25, 2007·The Journal of Clinical Investigation·Diego F CalvisiSnorri S Thorgeirsson
Apr 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Hun-Way HwangJoshua T Mendell
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Shih-Shih ChenChristoph Plass
Jul 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eric W JosephNeal Rosen
Sep 14, 2010·Cancer Cell·Mark E HatleyEric N Olson
Aug 9, 2013·Blood·Vipul ShuklaRunqing Lu
Aug 22, 2013·Molecular Cancer Therapeutics·Nagendra K ChaturvediShantaram S Joshi
May 30, 2014·The New England Journal of Medicine·Richard R FurmanY Lynn Wang
Oct 21, 2014·The Journal of Clinical Investigation·Niuscha YaktapourRobert Zeiser

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Citations

Sep 9, 2017·Leukemia & Lymphoma·Ashima ShuklaShantaram S Joshi
Mar 16, 2019·Cancer Science·Tetsuro Kawazoe, Koji Taniguchi
Nov 23, 2018·Cell Death & Disease·Qiuyan ZhaoBaiwen Li
Mar 5, 2018·Experimental Eye Research·Guannan ZhaoFrank J Lovicu
May 6, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·George J A Ten BoschJon D Laman

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