Steroid effects on ZAP-70 and SYK in relation to apoptosis in poor prognosis chronic lymphocytic leukemia
| Autor: | Marc Bracke, Mireille Van Gele, Lara Derycke, Femke Van Bockstaele, Fritz Offner, Ann Janssens, Jan Philippé, Barbara Vanhoecke, Sofie Lust, Jerina Boelens |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Chronic lymphocytic leukemia B-cell receptor Down-Regulation Syk Apoptosis chemical and pharmacologic phenomena Biology Methylprednisolone Gene Expression Regulation Enzymologic Glucocorticoid receptor Downregulation and upregulation Adrenal Cortex Hormones immune system diseases hemic and lymphatic diseases medicine Humans Syk Kinase RNA Messenger RNA Neoplasm Annexin A5 ZAP-70 Protein-Tyrosine Kinase Reverse Transcriptase Polymerase Chain Reaction Kinase Intracellular Signaling Peptides and Proteins hemic and immune systems Hematology Protein-Tyrosine Kinases Flow Cytometry Prognosis medicine.disease Leukemia Lymphocytic Chronic B-Cell Oncology Immunology Cancer research Chlorambucil Tyrosine kinase Vidarabine hormones hormone substitutes and hormone antagonists Plasmids |
| Zdroj: | Leukemia Research. 33:1335-1343 |
| ISSN: | 0145-2126 |
| DOI: | 10.1016/j.leukres.2009.02.022 |
| Popis: | There is resurgent interest in glucocorticoids (GCs) in the treatment of poor prognosis chronic lymphocytic leukemia (CLL). Little is known however on how GCs induce apoptosis in CLL. Methylprednisolone (MP) induces apoptosis in ZAP-70 positive CLL more readily than in ZAP-70 negative CLL, which is in contrast to the effects of radiation and chemotherapy. The increased GC sensitivity of ZAP-70+ CLL was studied in relation to the expression status of ZAP-70 and the related signal transducing tyrosine kinase SYK. Both ZAP-70 and SYK were downregulated by GC treatment. Moreover, SYK was dephosphorylated by the phosphatase PTP1B of which the expression and translation levels were induced by GCs. Inhibition of PTP1B successfully restored ZAP-70 expression and SYK phosphorylation but did not interfere with GC-induced apoptosis. Therefore, the downregulation of ZAP-70 and P-SYK per se during treatment with GCs is not sufficient to induce apoptosis, and different mechanisms must therefore be responsible for the increased steroid sensitivity of ZAP-70+ CLL. |
| Databáze: | OpenAIRE |
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