Telomere length and telomerase activity: variations with advancing age and potential role in childhood malignancies.

Telomeres, representing the chromosome nucleoprotein tails, shorten during each cell division due to the inability of conventional DNA polymerases to completely replicate the chromosome termini. When telomeres become critically short, cells are directed to exit from the cell division cycle (replicative senescence). Telomerase is a reverse transcriptase that synthesizes telomeric sequences, thereby prolonging the lifespan of cells. Telomere length and telomerase activity expression vary significantly in different normal somatic tissues and age groups. In many childhood malignancies (ie, acute leukemias and solid tumors), telomere length and telomerase activity of the malignant cell population may be correlated with the disease outcome and thus may be promising tools in evaluating prognosis and monitoring treatment progress. Finally, telomerase inhibition by using several strategies (ie, antisense oligonucleotides) represents a potentially valuable target for antitumor therapy in the near future.

Telomere length variation and telomerase activity expression in patients with congenital and acquired aplastic anemia.

Telomeres represent the nucleoprotein tails of chromosomes that get shortened with each cell division. When the telomere length reaches a critical point, cell senescence and death occur. Telomerase is a reverse transcriptase that counteracts telomere loss by adding telomeric sequences. In patients with acquired aplastic anemia, the mean telomere length (TRF) of peripheral blood leukocytes is generally short when compared to normal controls, without it being clear whether a relationship between TRF and disease severity exists. Additionally, increased telomerase activity (TA) is found in the bone marrow mononuclear cell population (MNCs) of aplastic anemia patients, especially in the chronic form of the disease. Fanconi anemia (FA) patients generally demonstrate increased TA and short telomeres in peripheral blood MNCs, a fact attributed to the high turnover of hematopoietic progenitor cells in combination with direct breakages at telomeric sequences. Furthermore, a strong correlation has been shown between TRF and the severity of aplastic anemia, but not with FA evolution towards myelodysplastic syndrome or acute myeloblastic leukemia. In respect of dyskeratosis congenita (DC), a disease of either X-linked or autosomal dominant/recessive inheritance which is characterized by premature ageing of highly regenerative tissues, studies have been carried out in order to elucidate whether the X-linked DC is caused by a defect in ribosomal RNA processing and/or telomere maintenance. Finally, the direct genetic link established between DC pathogenesis and short telomeres may lead to the development of new therapeutic protocols for diseases characterized by short telomere length and subsequent genomic instability.