dc.contributor.author | Krysov, S | en_US |
dc.contributor.author | Dias, S | en_US |
dc.contributor.author | Paterson, A | en_US |
dc.contributor.author | Mockridge, CI | en_US |
dc.contributor.author | Potter, KN | en_US |
dc.contributor.author | Smith, K-A | en_US |
dc.contributor.author | Ashton-Key, M | en_US |
dc.contributor.author | Stevenson, FK | en_US |
dc.contributor.author | Packham, G | en_US |
dc.date.accessioned | 2024-01-08T16:43:32Z | |
dc.date.issued | 2012-01-05 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/93591 | |
dc.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. | en_US |
dc.format.extent | 170 - 179 | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Blood | en_US |
dc.subject | Blotting, Western | en_US |
dc.subject | Cell Cycle | en_US |
dc.subject | Cell Membrane | en_US |
dc.subject | Cell Proliferation | en_US |
dc.subject | Humans | en_US |
dc.subject | Immunoenzyme Techniques | en_US |
dc.subject | Immunoglobulin M | en_US |
dc.subject | Leukemia, Lymphocytic, Chronic, B-Cell | en_US |
dc.subject | MAP Kinase Kinase 1 | en_US |
dc.subject | MAP Kinase Kinase 2 | en_US |
dc.subject | Mitogen-Activated Protein Kinase 1 | en_US |
dc.subject | Mitogen-Activated Protein Kinase 3 | en_US |
dc.subject | Proto-Oncogene Proteins c-myc | en_US |
dc.subject | RNA, Messenger | en_US |
dc.subject | Real-Time Polymerase Chain Reaction | en_US |
dc.subject | Tumor Cells, Cultured | en_US |
dc.title | Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cells. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.1182/blood-2011-07-370403 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/22086413 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 119 | en_US |