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.
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.
Clinic for Pediatric Oncology, Heinrich Heine University of Duesseldorf, Duesseldorf, Germany. troeger@med.uni-duesseldorf.de
Anja
A
Troeger
Ludmila
L
Glouchkova
Birgit
B
Ackermann
Gabriele
G
Escherich
Roland
R
Meisel
Helmut
H
Hanenberg
Monique L
ML
den Boer
Rob
R
Pieters
Gritta E
GE
Janka-Schaub
Ulrich
U
Goebel
Hans-Juergen
HJ
Laws
Dagmar
D
Dilloo
D000293:Adolescent; D019013:CD40 Antigens / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D006801:Humans; D007223:Infant; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D015854:Up-Regulation / Q000235:genetics; D019014:fas Receptor / Q000235:genetics*
D019013:CD40 Antigens; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor