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 journalArticle

9 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Death Domain Receptors
B-Lymphoid Precursor Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Up-Regulation
Cells
Recurrence
Survival
Lymphocytes
Tumor Necrosis Factor Receptors
Leukocyte Count
Ligation
Blood
B-Lymphocytes
Antigens
Growth

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

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. / Troeger, Anja; Glouchkova, Ludmila; Ackermann, Birgit; Escherich, Gabriele; Meisel, Roland; Hanenberg, Helmut; Den Boer, Monique L.; Pieters, Rob; Janka-Schaub, Gritta E.; Goebel, Ulrich; Laws, Hans Juergen; Dilloo, Dagmar.

In: Blood, Vol. 112, No. 4, 15.08.2008, p. 1028-1034.

Research output: Contribution to journalArticle

Troeger, A, Glouchkova, L, Ackermann, B, Escherich, G, Meisel, R, Hanenberg, H, Den Boer, ML, Pieters, R, Janka-Schaub, GE, Goebel, U, Laws, HJ & Dilloo, D 2008, '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', Blood, vol. 112, no. 4, pp. 1028-1034. https://doi.org/10.1182/blood-2007-11-123315
Troeger, Anja ; Glouchkova, Ludmila ; Ackermann, Birgit ; Escherich, Gabriele ; Meisel, Roland ; Hanenberg, Helmut ; Den Boer, Monique L. ; Pieters, Rob ; Janka-Schaub, Gritta E. ; Goebel, Ulrich ; Laws, Hans Juergen ; Dilloo, Dagmar. / 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. In: Blood. 2008 ; Vol. 112, No. 4. pp. 1028-1034.
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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.",
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AU - Escherich, Gabriele

AU - Meisel, Roland

AU - Hanenberg, Helmut

AU - Den Boer, Monique L.

AU - Pieters, Rob

AU - Janka-Schaub, Gritta E.

AU - Goebel, Ulrich

AU - Laws, Hans Juergen

AU - Dilloo, Dagmar

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