Role of survivin splice variants in pediatric acute precursor B lymphoblastic leukemia
| Autor: | Hans-Jürgen Laws, Anja Tröger, H. Bülle, Dagmar Dilloo, N. Wethkamp, Meinolf Siepermann, Gabriele Escherich, C. Mahotka, G. E. Janka-Schaub, Ulrich Göbel |
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| Rok vydání: | 2007 |
| Předmět: |
Survivin
Apoptosis Biology Inhibitor of apoptosis Bioinformatics medicine.disease_cause Polymerase Chain Reaction Inhibitor of Apoptosis Proteins Cohort Studies Leukocyte Count Coumarins Risk Factors Precursor B-Cell Lymphoblastic Leukemia-Lymphoma medicine Humans Protein Isoforms splice RNA Messenger Child neoplasms Cellular localization Retrospective Studies Gene Expression Regulation Leukemic Reverse Transcriptase Polymerase Chain Reaction Alternative splicing Genetic Variation medicine.disease Prognosis Neoplasm Proteins Haematopoiesis Leukemia Pediatrics Perinatology and Child Health Carcinogenesis Microtubule-Associated Proteins |
| Zdroj: | Klinische Padiatrie. 219(3) |
| ISSN: | 0300-8630 |
| Popis: | 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. PATIENTS AND 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. CONCLUSION 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. |
| Databáze: | OpenAIRE |
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