Haematology / Oncology (Paediatrics)
Telomere Lengths in Pediatric Acute Lymphblastic Leukamia (ALL)
Telomeres are repetitive non-coding nucleotide sequences capping the termini of linear chromosomes. They play a pivotal role in cell replication during which they get lost. A ribonucleoprotein complex, the so-called telomerase, protects telomeres from degradation and conveys their regeneration after cell division. Thus, cell proliferation capacity is greatly dependent on telomere length and telomerase function. Shortened telomeres and high levels of telomerase activity as compared to normal cells are found in different cancers. This combination probably allows leukemic cells to continuously replicate despite marked telomeric shortening. For childhood acute lymphoblastic leukemia (ALL) and other pediatric malignancies, only very limited data on telomere lengths in different cell subsets is available. Telomere maintenance has become an important target of new therapies and recent studies show antiproliferative effects of genetic and pharmacological telomerase inhibition. In particular, Baerlocher and colleagues have shown that the telomerase inhibitor Imetelstat induced complete hematological remission in the majority of patients with Essential Thrombocythemia (ET).
In our study, the pilot phase of which is supported by “Grants-in-Aid” of the DBMR, we are planning to systematically determine telomere lengths from peripheral blood of pediatric patients with ALL at the Division of Paediatric Haematology/Oncology, Department of Paediatrics, Inselspital, Bern University Hospital. Measurements will be performed using multicolor flow-FISH system, a differentiated and sensitive method combining flow cytometry with fluorescence in situ hybridization allowing separate analyses of distinct cell subpopulations. This method is established and as part of a collaboration in this project accessible in the laboratory of Professor Gabriela Baerlocher at the Inselspital, Bern University Hospital. In addition to measurements at time of diagnosis, we are going to determine telomere lengths during therapy and in parallel assess telomerase activity. This would provide us with the opportunity to correlate telomere lengths and telomerase activity with other laboratory and clinical parameters, i. e. response to therapy. As a long term goal of this study, we would like to assess in vitro antiproliferative and thus more targeted therapeutic effects of telomerase inhibition in pediatric ALL.