The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-κB pathways in subtypes of diffuse large B-cell lymphoma
Open accessAbstract
The activated B cell–like (ABC) subgroup of diffuse large B-cell lymphoma (DLBCL) is characterized by constitutive activation of the nuclear factor-κB (NF-κB) pathway. In this study, we showed that the NF-κB pathway induced the expression of the cytokines interleukin (IL)-6 and IL-10 in ABC DLBCL cell lines, which also have high levels of total and phosphorylated signal transducer and activator of transcription (STAT) 3 protein, suggesting autocrine signaling. Using RNA interference for STAT3, we defined a gene expression signature of IL-6 and IL-10 signaling through STAT3. Based on this signature, we constructed a molecular predictor of STAT3 signaling that defined a subset of ABC DLBCL tumors with high expression of STAT3, IL-6, and/or IL-10 and their downstream targets. Although the STAT3-high and STAT3-low subsets had equivalent expression of genes that distinguish ABC DLBCL from germinal center B cell–like DLBCL, STAT3-high ABC DLBCLs had higher expression of signatures that reflected NF-κB activity, proliferation, and glycolysis. A small-molecule inhibitor of Janus kinase signaling, which blocked STAT3 signature expression, was toxic only for ABC DLBCL lines and synergized with an inhibitor of NF-κB signaling. These findings suggest that the biological interplay between the STAT3 and NF-κB pathways may be exploited for the treatments of a subset of ABC DLBCLs.
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Cites
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Self-citationAn inhibitor of Bcl-2 family proteins induces regression of solid tumours
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Oncogenically active MYD88 mutations in human lymphoma
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Metadata
- Authors
- Lam, L. T., Wright, G., Davis, R. E., Lenz, G., Farinha, P., Dang, L., Chan, J. W., Rosenwald, A., Gascoyne, R. D., & Staudt, L. M.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-04-01
- Volume
- 111
- Issue
- 7
- Pages
- 3701-3713
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2067637255
- Cited by
- 353
- References
- 60
- FWCI
- 9.53
- Type
- journal article
- Language
- en
- Open access
- green
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- Lam, L. T., Wright, G., Davis, R. E., Lenz, G., Farinha, P., Dang, L., Chan, J. W., Rosenwald, A., Gascoyne, R. D., & Staudt, L. M. (2008). Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-κB pathways in subtypes of diffuse large B-cell lymphoma. Blood. https://doi.org/10.1182/blood-2007-09-111948
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