The molecular mechanisms that determine disease progression and evolution in CLL are not completely known. Telomeres are usually short in CLL and their attrition may contribute to disease evolution. In addition, telomerase activity (TA) levels have also been associated with prognosis and response to treatment. In order to integrate telomere associated variables (TAV) in CLL disease management further studies with robust methodology are required.
Purified peripheral CD19 (+) B-cells from 19 healthy donors and 42 CLLs in different stages of disease were obtained from the National Bank of DNA (Salamanca, Spain). Samples were tested to determine full telomere length (TL) distribution- including percentage of short telomeres by a high throughput quantitative fluorescence in situ hybridization (HT-Q-FISH) technique. TA by Quantitative Telomere Repeat Amplification Protocol (Q-TRAP) was also quantified. Full statistical analysis of the results in the context of the clinical history of the patients was performed.
Data from the pilot, retrospective study stablished strong correlations between key CLL variables and the severity of the disease. Overall, TL was shorter and TA presented higher values compared to normal age-matched subjects. Interestingly longer TL was observed for all CLL patients with somatic hyper-mutation (SHM) that in turn, was associated with better prognosis. Concomitantly, TA was elevated in those patients with no SHM and was linked to poor response to treatment and negative prognosis. The percentage of short telomeres was significantly higher for Binet C/Rai III and IV cases.
The use of reliable technologies to measure TAV should be integrated during early diagnostic in CLL to enhance the ability to predict disease evolution. This will require larger, prospective, longitudinal clinical studies.
Clinical trial identification
Legal entity responsible for the study
Life Length S.L.
Life Length S.L.
N. De Pedro, M. Diez, I. Garcia, R. González, B. Garcia, L. Esteban, L. Otero, P. Najarro, J.C. Estrada, J. García: Employee of Life Length. M. Chiesa: Former employee of Life Length.