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

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

0006-4971
170-179
Krysov, Sergey
3a78eac1-af40-4b37-8576-3462947649be
Dias, S.
f68ad193-3000-414c-9e72-aea5fd99a016
Paterson, A.
0a9ef773-a7e7-4584-9c3c-db15754c3bd6
Mockridge, C. Ian
327aef17-4837-4f2a-a93b-3d17cd1a7f9f
Potter, Kathleen N.
86a99047-494b-405b-a3f7-650c1dcd5838
Smith, Katherine C.
f0009a02-7453-4dfd-b6df-a9a46c676561
Ashton-Key, Margaret
5994ca63-021e-44b1-86c4-b7ae53321101
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Krysov, Sergey
3a78eac1-af40-4b37-8576-3462947649be
Dias, S.
f68ad193-3000-414c-9e72-aea5fd99a016
Paterson, A.
0a9ef773-a7e7-4584-9c3c-db15754c3bd6
Mockridge, C. Ian
327aef17-4837-4f2a-a93b-3d17cd1a7f9f
Potter, Kathleen N.
86a99047-494b-405b-a3f7-650c1dcd5838
Smith, Katherine C.
f0009a02-7453-4dfd-b6df-a9a46c676561
Ashton-Key, Margaret
5994ca63-021e-44b1-86c4-b7ae53321101
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394

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), 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: https://eprints.soton.ac.uk/id/eprint/339297
ISSN: 0006-4971
PURE UUID: 1eace1fe-c168-438a-8098-e07e2165245d
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 28 May 2012 14:07
Last modified: 31 Jan 2019 01:37

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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 ORCID iD

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