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Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cells

Krysov, Sergey, Dias, S., Paterson, A., Mockridge, C. Ian, Potter, Kathleen N., Smith, Katherine C., Ashton-Key, Margaret, Stevenson, Freda K. and Packham, Graham (2012) Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cells Blood, 119, (1), pp. 170-179. (doi:10.1182/blood-2011-07-370403). (PMID:22086413).

Record type: Article

Abstract

Although long considered as a disease of failed apoptosis, it is now clear that chronic lymphocytic leukemia (CLL) cells undergo extensive cell division in vivo, especially in progressive disease. Signaling via the B-cell receptor is thought to activate proliferation and survival pathways in CLL cells and also has been linked to poor outcome. Here, we have analyzed the expression of the proto-oncoprotein MYC, an essential positive regulator of the cell cycle, after stimulation of surface IgM (sIgM). MYC expression was rapidly increased after sIgM stimulation in a subset of CLL samples. The ability of sIgM stimulation to increase MYC expression was correlated with sIgM-induced intracellular calcium fluxes. MYC induction was partially dependent on the MEK/ERK signaling pathway, and MYC and phosphorylated ERK1/2 were both expressed within proliferation centers in vivo. Although stimulation of sIgD also resulted in ERK1/2 phosphorylation, responses were relatively short lived compared with sIgM and were associated with significantly reduced MYC induction, suggesting that the kinetics of ERK1/2 activation is a critical determinant of MYC induction. Our results suggest that ERK1/2-dependent induction of MYC is likely to play an important role in antigen-induced CLL cell proliferation.

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More information

e-pub ahead of print date: 15 November 2011
Published date: 5 January 2012
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 339297
URI: http://eprints.soton.ac.uk/id/eprint/339297
ISSN: 0006-4971
PURE UUID: 1eace1fe-c168-438a-8098-e07e2165245d

Catalogue record

Date deposited: 28 May 2012 14:07
Last modified: 01 Sep 2017 16:32

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Contributors

Author: Sergey Krysov
Author: S. Dias
Author: A. Paterson
Author: C. Ian Mockridge
Author: Katherine C. Smith
Author: Margaret Ashton-Key
Author: Graham Packham

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