title: High nerve growth factor receptor (p75NTR) expression is a favourable prognostic factor in paediatric B cell precursor-acute lymphoblastic leukaemia.
abstract: 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.
authors.affiliation: Clinic for Paediatric Haematology, Oncology and Immunology, Heinrich Heine University, Duesseldorf, Germany. troeger@med.uni-duesseldorf.de
authors.forename: Anja
authors.initials: A
authors.lastname: Troeger
authors.forename: Sonja
authors.initials: S
authors.lastname: Gudowius
authors.forename: Gabriele
authors.initials: G
authors.lastname: Escherich
authors.forename: Monique L
authors.initials: ML
authors.lastname: den Boer
authors.forename: Ludmila
authors.initials: L
authors.lastname: Glouchkova
authors.forename: Birgit
authors.initials: B
authors.lastname: Ackermann
authors.forename: Roland
authors.initials: R
authors.lastname: Meisel
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Laws
authors.forename: Marketa
authors.initials: M
authors.lastname: Groeger
authors.forename: Ruediger
authors.initials: R
authors.lastname: Wessalowski
authors.forename: Reinhart
authors.initials: R
authors.lastname: Willers
authors.forename: Jochen
authors.initials: J
authors.lastname: Harbott
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Ulrich
authors.initials: U
authors.lastname: Goebel
authors.forename: Gritta E
authors.initials: GE
authors.lastname: Janka-Schaub
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.forename: Dagmar
authors.initials: D
authors.lastname: Dilloo
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; C484065:NGFR protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor