Diagnostics, Prognostic and Therapeutic Exploitation of Telomeres and Telomerase in Leukemias

Telomeres are specialized structures at the end of human chromosomes. Telomere length decreases with eachcell division, thus, reflecting the mitotic history of somatic cells. Telomerase, the ribonucleoprotein enzyme which main-tains telomeres of eukaryotic chromosomes, is up-regulated in the vast majority of human neoplasia but not in normal so-matic tissues. In contrast to other somatic cells, normal primitive human hematopoietic cells and some peripheral bloodcells expressed low levels of telomerase activity. This activity is thought to play an important role in self-renewal of he-matopoietic stem cells. In malignant disorders, telomere lengths are generally shortened and telomerase expression andactivity enhanced with high differences in the levels. Although it is necessary to be cautious in interpreting these data,there are indications that telomere length and telomerase expression and activity can serve as a molecular marker of theclinical progression and prognosis of most leukemias. Approaches that directly target telomerase, telomeres or telomeraseregulatory mechanisms have been developed. Some of these anti-telomerase strategies in combination with conventionaldrugs proved to be promising in some types of leukemias.