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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1028-1034. Prepublished online as a Blood First Edition Paper on June 13, 2008; DOI 10.1182/blood-2007-11-123315. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-123315v1 112/4/1028    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Troeger, A. Articles by Dilloo, D. Search for Related Content PubMed PubMed Citation Articles by Troeger, A. Articles by Dilloo, D. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS High expression of CD40 on B-cell precursor acute lymphoblastic leukemia blasts is an independent risk factor associated with improved survival and enhanced capacity to up-regulate the death receptor CD95 Anja Troeger1, Ludmila Glouchkova1, Birgit Ackermann1, Gabriele Escherich2, Roland Meisel1, Helmut Hanenberg1, Monique L. den Boer3, Rob Pieters3, Gritta E. Janka-Schaub2, Ulrich Goebel1, Hans-Juergen Laws1, and Dagmar Dilloo1 1 Clinic for Pediatric Oncology, Hematology, and Clinical Immunology, Heinrich Heine University of Duesseldorf, Duesseldorf, Germany; 2 Clinic for Pediatric Hematology and Oncology, University Hospital, Hamburg-Eppendorf, Germany; and 3 Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands CD40 and CD27, members of the tumor necrosis factor receptor (TNFR) family, are critical regulators of lymphocyte growth and differentiation. In B-cell precursor acute lymphoblastic leukemia (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. In addition, in multivariable analysis, a very high percentage of CD40+ 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 proapoptotic signals. Yet, although CD40 ligation does result in significant up-regulation of CD80/CD86 in our cohort, it is up-regulation of the death receptor CD95 that significantly correlates with the percentage of CD40+ blasts. Thus very high expression of CD40 on BCP-ALL blasts is an independent prognostic marker indicative of superior relapse-free survival that may in part be due to CD40-dependent death receptor up-regulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020