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), 170-179. (doi:10.1182/blood-2011-07-370403 ). (PMID:22086413).
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Description/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.
| Item Type: | Article |
|---|---|
| ISSNs: | 0006-4971 (print) 1528-0020 (electronic) |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine > Cancer Sciences |
| Item ID: | 339297 |
| Date Deposited: | 28 May 2012 14:07 |
| Last Modified: | 26 Jul 2012 00:51 |
| Contributors: | Krysov, Sergey (Author) Dias, S (Author) Paterson, A (Author) Mockridge, C. Ian (Author) Potter, Kathleen N. (Author) Smith, Katherine C. (Author) Ashton-Key, Margaret (Author) Stevenson, Freda K. (Author) Packham, Graham (Author) |
| Date: | 5 January 2012 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/339297 |
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