High nerve growth factor receptor (p75NTR) expression is a favourable prognostic factor in paediatric B cell precursor-acute lymphoblastic leukaemia.
Nerve growth factor (NGF) plays a pivotal role in cellular survival/death decisions with the low affinity receptor p75NTR predominately transmitting anti-proliferative signals. In spite of its established role in B-cell function and identification as a prognostically favourable marker in a number of malignancies, little is known about the expression pattern and prognostic significance of p75NTR in B cell precursor-acute lymphoblastic leukaemia (BCP-ALL). p75NTR expression was prospectively studied on primary ALL-blasts in a cohort of paediatric patients with common ALL (n = 86) and preB-ALL (n = 34) treated within the Co-operative study group for childhood acute lymphoblastic leukaemia (CoALL) protocol, CoALL06-97. Flow cytometric analysis showed that almost half of the patients expressed no or negligible amounts of p75NTR (<10%). The median expression in patients expressing p75NTR beyond that threshold was 49% (range 11-100%). In patients classified as low-risk at diagnosis, p75NTR expression was significantly higher than in high-risk patients (P = 0.001). Of note, p75NTR expression was lower in the 21 patients who subsequently developed relapse compared with those remaining in remission (P = 0.038). Accordingly, relapse-free survival was significantly better in patients expressing high surface p75NTR (P = 0.041). Thus, in this prospective analysis, high p75NTR expression was a strong prognostic marker that identified a group of paediatric ALL patients with favourable outcome.
Troeger
Anja
A
Clinic for Paediatric Haematology, Oncology and Immunology, Heinrich Heine University, Duesseldorf, Germany. troeger@med.uni-duesseldorf.de
Gudowius
Sonja
S
Escherich
Gabriele
G
den Boer
Monique L
ML
Glouchkova
Ludmila
L
Ackermann
Birgit
B
Meisel
Roland
R
Laws
Hans-Juergen
HJ
Groeger
Marketa
M
Wessalowski
Ruediger
R
Willers
Reinhart
R
Harbott
Jochen
J
Pieters
Rob
R
Goebel
Ulrich
U
Janka-Schaub
Gritta E
GE
Hanenberg
Helmut
H
Dilloo
Dagmar
D
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood; D009419:Nerve Tissue Proteins / Q000097:blood*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000628:therapy; D011379:Prognosis; D011446:Prospective Studies; D017475:Receptors, Nerve Growth Factor / Q000097:blood*; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C484065:NGFR protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor