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.