The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Constitutive Nuclear Factor κB Activity Is Required for Survival of Activated B Cell–like Diffuse Large B Cell Lymphoma Cells
Open accessAbstract
Gene expression profiling has revealed that diffuse large B cell lymphoma (DLBCL) consists of at least two distinct diseases. Patients with one DLBCL subtype, termed activated B cell–like (ABC) DLBCL, have a distinctly inferior prognosis. An untapped potential of gene expression profiling is its ability to identify pathogenic signaling pathways in cancer that are amenable to therapeutic attack. The gene expression profiles of ABC DLBCLs were notable for the high expression of target genes of the nuclear factor (NF)-κB transcription factors, raising the possibility that constitutive activity of the NF-κB pathway may contribute to the poor prognosis of these patients. Two cell line models of ABC DLBCL had high nuclear NF-κB DNA binding activity, constitutive IκB kinase (IKK) activity, and rapid IκBα degradation that was not seen in cell lines representing the other DLBCL subtype, germinal center B-like (GCB) DLBCL. Retroviral transduction of a super-repressor form of IκBα or dominant negative forms of IKKβ was toxic to ABC DLBCL cells but not GCB DLBCL cells. DNA content analysis showed that NF-κB inhibition caused both cell death and G1-phase growth arrest. These findings establish the NF-κB pathway as a new molecular target for drug development in the most clinically intractable subtype of DLBCL and demonstrate that the two DLBCL subtypes defined by gene expression profiling utilize distinct pathogenetic mechanisms.
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Cites
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Cited by
Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma
Davis, R. E., Ngo, V. N., Lenz, G., Tolar, P., Young, R. M., Romesser, P. B., Kohlhammer, H., Lamy, L., Zhao, H., Yang, Y., et al. (2010) · Nature · doi:10.1038/nature08638 · Cited by 1,643
Self-citationMechanisms of B-cell lymphoma pathogenesis
Küppers, R. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1589 · Cited by 965
Annunziata, C. M., Davis, R. E., Demchenko, Y., Bellamy, W., Gabrea, A., Zhan, F., Lenz, G., Hanamura, I., Wright, G., Xiao, W., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.07.004 · Cited by 952
Self-citationThe genetic architecture of multiple myeloma
Morgan, G. J., Walker, B. A., & Davies, F. E. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3257 · Cited by 913
Circuitry of nuclear factor κB signaling
Hoffmann, A., & Baltimore, D. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00375.x · Cited by 907
Metadata
- Authors
- Davis, R. E., Brown, K. D., Siebenlist, U., & Staudt, L. M.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2001-12-17
- Volume
- 194
- Issue
- 12
- Pages
- 1861-1874
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2136426653
- Cited by
- 1,051
- References
- 68
- FWCI
- 12.37
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Davis, R. E., Brown, K. D., Siebenlist, U., & Staudt, L. M. (2001). Constitutive Nuclear Factor κB Activity Is Required for Survival of Activated B Cell–like Diffuse Large B Cell Lymphoma Cells. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.194.12.1861
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