Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia.
OBJECTIVE
Impaired apoptosis, mediated by members of the inhibitor of apoptosis proteins (IAP) family such as survivin, is thought to contribute to leukemic cell survival. In contrast to low expression of survivin in normal differentiated adult tissues, very high levels of survivin have been described in a number of different tumors. Overexpression of survivin was found to correlate with poor prognosis in a variety of cancers including hematologic malignancies. To date, however, there is no information available on the prognostic role of survivin in pediatric precursor B-cell acute lymphocytic leukemia (BCP-ALL), the most frequent malignancy in childhood.


METHODS
In a retrospective study including 66 pediatric patients we analyzed the impact of survivin protein levels on outcome in BCP-ALL.


RESULTS
Survivin overexpression, with an up to ten-fold increase of the normal level, was detected in 65% of the leukemic samples in contrast to negligible expression in non-malignant hematopoietic cells. Despite considerable variety of expression levels in ALL cells, there was no association of survivin levels with established risk factors. However, patients suffering relapse of disease or death had significantly higher survivin expression than those with a favorable outcome. Overexpression of survivin is a significant prognostic marker for 3 year relapse free, event-free and overall survival, again independent of the established prognostic factors in ALL, such as age and leukocyte count at diagnosis as assessed in multivariate analysis.


CONCLUSIONS
Overexpression of survivin in BCP-ALL identifies patients with a high risk of early relapse. Upon confirmation in a prospective analysis, survivin expression may, in the future, serve to further refine treatment stratification with intensification of therapy in those patients prone to relapse.
Troeger
Anja
A
Clinic for Pediatric Oncology, Hematology and Immunology, University of Duesseldorf, Duesseldorf, Germany. troeger@med.uni-duesseldorf.de
Siepermann
Meinolf
M
Escherich
Gabriele
G
Meisel
Roland
R
Willers
Reinhardt
R
Gudowius
Sonja
S
Moritz
Thomas
T
Laws
Hans-Juergen
HJ
Hanenberg
Helmut
H
Goebel
Ulrich
U
Janka-Schaub
Gritta E
GE
Mahotka
Csaba
C
Dilloo
Dagmar
D
D000293:Adolescent; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis* / Q000502:physiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis* / Q000502:physiology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000473:pathology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D000077022:Survivin; D016896:Treatment Outcome
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin