CD154 expression triggered by purine analogues in vitro: Correlation with treatment response and autoimmune events in chronic lymphocytic leukemia
| Autor: | M. J. Citores, José A. García-Marco, Juan A. Vargas, Mercedes Villarreal, Raquel Castejón, Silvia Rosado |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research Chronic lymphocytic leukemia CD40 Ligand Purine analogue Antineoplastic Agents Autoimmunity medicine.disease_cause Peripheral blood mononuclear cell Immunophenotyping immune system diseases Outcome Assessment Health Care Genetics medicine Humans CD154 Molecular Biology Cells Cultured Aged Aged 80 and over business.industry hemic and immune systems Cell Biology Hematology Middle Aged medicine.disease Flow Cytometry Prognosis Leukemia Lymphocytic Chronic B-Cell In vitro Fludarabine Apoptosis Immunology Cladribine Female business Vidarabine medicine.drug |
| Zdroj: | Experimental hematology. 38(3) |
| ISSN: | 1873-2399 |
| Popis: | Despite a fludarabine-based treatment is the first choice of therapy in chronic lymphocytic leukemia (CLL), not all patients achieve a partial or complete response and some of them develop autoimmune manifestations. The aim of this study was to evaluate the influence of CD154 on these adverse effects because CD154 is involved in both B-cell survival and autoimmunity.Peripheral blood mononuclear cells (PBMC) from 36 patients with CLL were cultured in vitro with fludarabine or 2-chlorodeoxyadenosine for 24, 48, and 72 hours.Seven patients (19.4%) presented CD154 expression in PBMC cultured with purine analogues in vitro for 24 and/or 48 hours, while no expression was found when cultured in media alone. These seven patients showed a decreased apoptotic rate in vitro after purine analogues compared with those patients who did not express CD154 (p = 0.01 for fludarabine; p0.001 for 2-chlorodeoxyadenosine). CD154 expression was found to have prognostic value for response to fludarabine in vivo and was associated with the development of autoimmune manifestations (odds ratio = 25; 95% confidence interval = 3.5-166.7; p0.001).Our preliminary results suggest that CD154 expression in CLL patients, which may be induced by purine analogues, is associated with resistance to fludarabine and with development of autoimmune manifestations. |
| Databáze: | OpenAIRE |
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