title: Telomeres, Telomerase and Leukaemia.
abstract: There is increasing evidence supporting the hypothesis that telomere shortening both in vitro and in vivo is the clock that counts cell divisions and determines the onset of cellular senescence. Cells overcome the senescence mechanisms by stabilising telomere length, probably due to the activity of telomerase that specifically elongates telomeres. The striking observation that almost all malignant cancers have telomerase activity indicate that there is intensive selective pressure of telomerase activation with the progression of malignancy. Indirect support for this view is that benign or pre-cancerous lesions are telomerase silent. The fact that telomerase activity is observed in over 85% of human primary malignancies raises the possibilities that it may be a new marker of cancer with diagnostic and therapeutic potentials. Can such ideas be applied to leukaemias and preleukaemias? Since normal haematopoietic stem cells and their progeny express telomerase activity, it is important to consider whether or not telomere shortening and telomerase activity play any role in leukaemic progression. Telomere reduction has been observed in various leukaemias including in ALL, AML, transformed leukaemias from MDS and late stage of CML and CLL and might be indicative of the length of the disease. Elevated telomerase activity has also been found in ALL, AML, CML and CLL. In AML, patients with chromosomal abnormalities 11q, -5, -7 had higher telomerase activity and unfavourable prognosis; while those with favourable cytogenetics such as t(8:21), inversion 16 showed low levels of telomerase. This suggests that telomerase activity may be a marker for poor prognosis of AML. Unanswered at present is the potential role of telomeres and telomerase in the progression of benign to malignant tumours. Further studies on the expression and regulation of the individual components of telomerase may enable us to clarify the diagnostic and therapeutic potential of telomerase in leukaemias.
authors.affiliation: a Department of Haematology , St Bartholomew's and the Royal London School of Medicine and Dentistry , Turner St, London El 2AD , U.K.
authors.forename: X R
authors.initials: XR
authors.lastname: Jiang
authors.affiliation: a Department of Haematology , St Bartholomew's and the Royal London School of Medicine and Dentistry , Turner St, London El 2AD , U.K.
authors.forename: S M
authors.initials: SM
authors.lastname: Kelsey
authors.affiliation: a Department of Haematology , St Bartholomew's and the Royal London School of Medicine and Dentistry , Turner St, London El 2AD , U.K.
authors.forename: A C
authors.initials: AC
authors.lastname: Newland
keywords: Leukaemia; Telomerase; Telomere