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

Deville, Laure; Hillion, Josette; Lanotte, Michel; Rousselot, Philippe; S�gal-Bendirdjian, Evelyne
June 2006
Current Pharmaceutical Biotechnology;Jun2006, Vol. 7 Issue 3, p171
Academic Journal
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.


Related Articles

  • Alternative lengthening of telomeres is associated with chromosomal instability in osteosarcomas. Scheel, Christina; Schaefer, Karl-Ludwig; Jauch, Anna; Keller, Monika; Wai, Daniel; Brinkschmidt, Christian; van Valen, Frans; Boecker, Werner; Dockhorn-Dworniczak, Barbara; Poremba, Christopher // Oncogene;6/28/2001, Vol. 20 Issue 29, p3835 

    Telomere maintenance is regarded as a key mechanism in overcoming cellular senescence in tumor cells and in most cases is achieved by the activation of telomerase. However there is at least one alternative mechanism of telomere lengthening (ALT) which is characterized by heterogeneous and...

  • The plasticity of human telomeres demonstrated by a hypervariable telomere repeat array that is located on some copies of 16p and 16q. Coleman, Joanna; Baird, Duncan M.; Royle, Nicola J. // Human Molecular Genetics;Sep99, Vol. 8 Issue 9, p1637 

    Studies the plasticity of human telomeres demonstrated by a hypervariable telomere repeat array located on some copies of 16p and 16q regions of the chromosome. Influence of telomerase activity on telomere repeats at the proximal end of the array; Distribution of subterminal repeat sequences on...

  • Senescence: does it all happen at the ends? Stewart, Sheila A; Weinberg, Robert A // Oncogene;1/21/2002 Review, Vol. 21 Issue 4, p627 

    Over 60 years ago Barbara McClintock described the telomere and suggested that it protected the chromosome from illegitimate or end-to-end fusion, thus functioning to protect the genome. Since that time we have discovered that the telomere is a complex structure composed of both DNA and a...

  • Many ways to telomere dysfunction: in vivo studies using mouse models. Goytisolo, Fermín A; Blasco, María A // Oncogene;1/21/2002 Review, Vol. 21 Issue 4, p584 

    The existence of a capping structure at the extremities of chromosomes was first deduced in the 1930s by Herman Müller (Müller, 1938), who showed that X-irradiation of Drosophila rarely resulted in terminal deletions or inversions of chromosomes, suggesting that chromosome ends have...

  • Telomeres: Taking the measure. Lundblad, Vicki // Nature;6/26/2003, Vol. 423 Issue 6943, p926 

    Cites findings of the study which describes crucial feature of the process by which telomerase can sense and regulate the length of individual chromosome ends called telomers. Importance of preserving telomeres; Ways in which specialized protein complexes preserve telomeres; Components of...

  • Telomeres and telomerase in hematologic neoplasia. Ohyashiki, Junko H; Sashida, Goro; Tauchi, Tetsuzo; Ohyashiki, Kazuma // Oncogene;1/21/2002 Review, Vol. 21 Issue 4, p680 

    Normal hematopoietic cells express telomerase activity, however the presence of telomerase does not necessarily imply stable and thus unchanging telomere length. Gradual telomere loss with aging and rapid cycling of hematopoietic stem cells might contribute to immunosenescence, exhausted...

  • Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita. Parry, Erin M.; Alder, Jonathan K.; Lee, Stella S.; Phillips III, John A.; Loyd, James E.; Duggal, Priya; Armanios, Mary // Journal of Medical Genetics;May2011, Vol. 48 Issue 5, p327 

    Dyskeratosis congenita (DC) is a premature ageing syndrome characterised by short telomeres. An X-linked form of DC is caused by mutations in DKC1 which encodes dyskerin, a telomerase component that is essential for telomerase RNA stability. However, mutations in DKC1 are identifiable in only...

  • Mechanisms and regulation of DNA end resection. Longhese, Maria Pia; Bonetti, Diego; Manfrini, Nicola; Clerici, Michela // EMBO Journal;9/1/2010, Vol. 29 Issue 17, p2864 

    DNA double-strand breaks (DSBs) are highly hazardous for genome integrity, because failure to repair these lesions can lead to genomic instability. DSBs can arise accidentally at unpredictable locations into the genome, but they are also normal intermediates in meiotic recombination. Moreover,...

  • Developmentally regulated initiation of DNA synthesis by telomerase: evidence for factor-assisted de novo telomere formation. Bednenko, Janna; Melek, Meni; Greene, Eric C.; Shippen, Dorothy E. // EMBO Journal;5/1/1997, Vol. 16 Issue 9, p2507 

    Telomerase serves a dual role at telomeres, maintaining tracts of telomere repeats and forming telomeres de novo on broken chromosomes in a process called chromosome healing. In ciliates, both mechanisms are readily observed. Vegetatively growing cells maintain pre-existing telomeres, while...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics