CD154 expression triggered by purine analogues in vitro: Correlation with treatment response and autoimmune events in chronic lymphocytic leukemia
Received 19 August 2009; received in revised form 14 December 2009; accepted 14 December 2009. published online 21 December 2009.
Objective
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.
Materials and Methods
Peripheral blood mononuclear cells (PBMC) from 36 patients with CLL were cultured in vitro with fludarabine or 2-chlorodeoxyadenosine for 24, 48, and 72hours.
Results
Seven patients (19.4%) presented CD154 expression in PBMC cultured with purine analogues in vitro for 24 and/or 48hours, 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; p<0.001 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; p<0.001).
Conclusion
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.
aServicio de Medicina Interna, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, Spain
bServicio de Hematología, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, Spain
Offprint requests to: Maria Jesus Citores, Ph.D., Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Joaquín Rodrigo 2, 28222 Majadahonda, Madrid, Spain
ABSTRACT