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 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, Dagmar Dilloo

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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 pro-apoptotic 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.

Original languageEnglish (US)
Pages (from-to)1028-1034
Number of pages7
JournalBlood
Volume112
Issue number4
DOIs
StatePublished - Aug 15 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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