Submitted November 15, 2007
Accepted May 28, 2008
High expression of CD40 on BCP-ALL blasts is an independent risk factor associated with improved survival and enhanced capacity to upregulate the death receptor CD95
Anja Troeger*, Ludmila Glouchkova, Birgit Ackermann, Gabriele Escherich, Roland Meisel, Helmut Hanenberg, Monique L. den Boer, Rob Pieters, Gritta E Janka-Schaub, Ulrich Goebel, Hans-Juergen Laws, and Dagmar Dilloo
Clinic for Pediatric Oncology, Hematology and Clinical Immunology, University Hospital, Duesseldorf, Germany
Clinic for Pediatric Hematology and Oncology, University Hospital, Hamburg-Eppendorf, Germany
Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, Netherlands
* Corresponding author; email: troeger{at}med.uni-duesseldorf.de.
CD40 and CD27, members of the tumour necrosis factor receptor (TNFR) family, are critical regulators of lymphocyte growth and differentiation. In B cell precursor (BCP)-ALL, we prospectively assessed the impact of CD40 and CD27 on outcome in 121 children treated according to the CoALL06-97 protocol. Expression of both CD40 and CD27 was found to be significantly higher in low than in high risk patients as defined by standard clinical risk parameters such as age and white blood cell count. Also in multivariable analysis a very high percentage of CD40 positive blasts at diagnosis was identified as an independent favorable prognostic factor for relapse free survival. Of note, high CD40 expression particularly protected against late relapse. In B cells, CD40 is known to enhance both antigen-presenting capacity and sensitivity to pro-apoptotic signals. Yet, although CD40-ligation does result in significant upregulation of CD80/CD86 in our cohort, it is upregulation of the death receptor CD95 that significantly correlates with the percentage of CD40 positive blasts. Thus very high expression of CD40 on BCP-ALL blasts is an independent prognostic marker indicative of superior relapse free survival which may in part be due to CD40 dependent death receptor upregulation.
