Role of survivin splice variants in pediatric acute precursor B lymphoblastic leukemia.
BACKGROUND
Survivin, a member of the inhibitor of apoptosis protein (IAP) family is transiently expressed at low levels during normal hematopoesis but profoundly overexpressed in adult leukemia potentially contributing to leukemogenesis due to deregulated apoptosis and defective cell cycle control. Alternative splicing results in four different mRNA variants survivin, survivin2B, survivin-DeltaExon3 and survivin-3B, with distinct cellular localization patterns and anti-apoptotic potential. Due to co-localization of survivin and survivin-2B in the cytoplasm survivin-2B may permit interactive fine-tuning of survivin actions and moreover play an attenuating role in its anti-apoptotic function. Lack of survivin-2B is associated with disease progression of malignomas suggesting a differential role of these isoforms in tumorigenesis.


METHODS
We therefore determined the expression of the functional survivin splice variants performing RT- and real-time PCR in a purely pediatric cohort of 20 patients suffering from precursor B-ALL (BCP-ALL).


RESULTS
Here, we demonstrate for the first time in pediatric patients with precursor B-ALL an association between lower survivin-2B expression and affiliation to the high risk group.


CONCLUSIONS
The idea that survivin-2B may act as natural antagonist of survivin could potentially be used in novel approaches of anti-cancer treatment by influencing the proportional expression of the different splice variants.
Tröger
A
A
Clinic for Pediatric-Oncology, -Hematology and Clinical Immunology, Heinrich Heine University Duesseldorf, Moorenstrasse 5, 40225 Düsseldorf. troeger@med.uni-duesseldorf.de
Siepermann
M
M
Mahotka
C
C
Wethkamp
N
N
Bülle
H
H
Laws
H-J
HJ
Escherich
G
G
Janka-Schaub
G
G
Göbel
U
U
Dilloo
D
D
D017209:Apoptosis / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D003374:Coumarins; D015973:Gene Expression Regulation, Leukemic; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007958:Leukocyte Count; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D000077022:Survivin
C107489:BIRC5 protein, human; D003374:Coumarins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D000077022:Survivin; C014922:W10294A