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Aberrantly activated anti‐apoptotic signalling mechanisms in chronic lymphocytic leukaemia cells: clues to the identification of novel therapeutic targets

Gitendra Wickremasinghe, R. ; Prentice, Archibald G. ; Steele, Andrew J.

British journal of haematology, 2011-06, Vol.153 (5), p.545-556 [Periódico revisado por pares]

Oxford, UK: Blackwell Publishing Ltd

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Título:
Aberrantly activated anti‐apoptotic signalling mechanisms in chronic lymphocytic leukaemia cells: clues to the identification of novel therapeutic targets
Autor: Gitendra Wickremasinghe, R. ; Prentice, Archibald G. ; Steele, Andrew J.
Assuntos: AKT protein ; Animal models ; Antibodies ; Antineoplastic Agents - pharmacology ; apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Biological and medical sciences ; Chemotherapy ; Chronic lymphatic leukemia ; chronic lymphocytic leukaemia ; chronic lymphocytic leukaemia drug sensitivity ; Clinical trials ; Cytotoxicity ; Enzyme Activation - physiology ; Enzyme Inhibitors - pharmacology ; Extracellular signal-regulated kinase ; Hematologic and hematopoietic diseases ; Humans ; Intracellular Signaling Peptides and Proteins - metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell - enzymology ; Leukemia, Lymphocytic, Chronic, B-Cell - pathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Malignancy ; Medical sciences ; Molecular Targeted Therapy - methods ; Protein kinase C ; protein phosphorylation ; Protein-tyrosine kinase ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Protein-Tyrosine Kinases - metabolism ; Signal transduction ; Signal Transduction - physiology ; src-Family Kinases - metabolism ; Syk Kinase ; trials
É parte de: British journal of haematology, 2011-06, Vol.153 (5), p.545-556
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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Descrição: Summary 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.
Editor: Oxford, UK: Blackwell Publishing Ltd
Idioma: Inglês

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Aberrantly activated anti‐apoptotic signalling mechanisms in chronic lymphocytic leukaemia cells: clues to the identification of novel therapeutic targets

Gitendra Wickremasinghe, R. ; Prentice, Archibald G. ; Steele, Andrew J.

Oxford, UK: Blackwell Publishing Ltd

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