The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Network model of survival signaling in large granular lymphocyte leukemia
Open accessAbstract
T cell large granular lymphocyte (T-LGL) leukemia features a clonal expansion of antigen-primed, competent, cytotoxic T lymphocytes (CTL). To systematically understand signaling components that determine the survival of CTL in T-LGL leukemia, we constructed a T-LGL survival signaling network by integrating the signaling pathways involved in normal CTL activation and the known deregulations of survival signaling in leukemic T-LGL. This network was subsequently translated into a predictive, discrete, dynamic model. Our model suggests that the persistence of IL-15 and PDGF is sufficient to reproduce all known deregulations in leukemic T-LGL. This finding leads to the following predictions: ( i ) Inhibiting PDGF signaling induces apoptosis in leukemic T-LGL. ( ii ) Sphingosine kinase 1 and NFκB are essential for the long-term survival of CTL in T-LGL leukemia. ( iii ) NFκB functions downstream of PI3K and prevents apoptosis through maintaining the expression of myeloid cell leukemia sequence 1. ( iv ) T box expressed in T cells (T-bet) should be constitutively activated concurrently with NFκB activation to reproduce the leukemic T-LGL phenotype. We validated these predictions experimentally. Our study provides a model describing the signaling network involved in maintaining the long-term survival of competent CTL in humans. The model will be useful in identifying potential therapeutic targets for T-LGL leukemia and generating long-term competent CTL necessary for tumor and cancer vaccine development.
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Boolean network simulations for life scientists
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Self-citationDiscovery of somatic STAT5b mutations in large granular lymphocytic leukemia
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Metadata
- Authors
- Zhang, R., Shah, M. V., Yang, J., Nyland, S. B., Liu, X., Yun, J. K., Albert, R., & Loughran, T. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-10-21
- Volume
- 105
- Issue
- 42
- Pages
- 16308-16313
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2151852639
- Cited by
- 375
- References
- 36
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- green
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