Aberrantly activated anti-apoptotic signalling mechanisms in chronic lymphocytic leukaemia cells: clues to the identification of novel therapeutic targets
| Autor: | Archibald G. Prentice, R. Gitendra Wickremasinghe, Andrew J. Steele |
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| Rok vydání: | 2011 |
| Předmět: |
MAPK/ERK pathway
Antineoplastic Agents Apoptosis mTORC1 Receptor tyrosine kinase hemic and lymphatic diseases Humans Syk Kinase Medicine Molecular Targeted Therapy Enzyme Inhibitors Protein kinase A Protein kinase B Protein kinase C biology business.industry Kinase Intracellular Signaling Peptides and Proteins Hematology Protein-Tyrosine Kinases Leukemia Lymphocytic Chronic B-Cell Enzyme Activation src-Family Kinases Immunology biology.protein Cancer research Signal transduction business Signal Transduction |
| Zdroj: | British Journal of Haematology. 153:545-556 |
| ISSN: | 0007-1048 |
| DOI: | 10.1111/j.1365-2141.2011.08676.x |
| Popis: | Chronic lymphocytic leukaemia (CLL) is the commonest haematological malignancy in the western world and is incurable by cytotoxic therapy. Considerable research effort has identified the signal transduction pathways in CLL cells that contribute to anti-apoptotic signalling. Some pathways are constitutively activated in CLL cells but upregulated in normal cells only when protein tyrosine kinases (PTKs) are activated by ligands. This review describes which PTKs are aberrantly activated in CLL cells and are potential targets for inhibition. Additional potential targets within pathways downstream of these PTKs include Mek/Erk, mTorc1, protein kinase C, PI-3 kinase/Akt, nuclear factor-κB and cyclin-dependent protein kinase. Numerous studies have identified chemical agents and antibodies that selectively kill CLL cells, irrespective of their genetic resistance to conventional chemotherapeutic agents, and which can overcome cytoprotective microenvironmental signalling. These studies have resulted in identification of novel therapies, some of which are currently undergoing clinical trials. In vitro and animal model studies and clinical trials could determine which inhibitors of which targets are the likely to be most effective and least toxic either singly or in combination. |
| Databáze: | OpenAIRE |
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