TELOMERES AND TELOMERASE IN NORMAL AND MALIGNANT HEMATOPOIETIC-CELLS

The normal haematopoietic system harbours telomerase-competent cells w ith a capacity to upregulate the activity to notable levels in a telom ere length-independent manner. Strong telomerase activity is found in progenitor stem cells and activated lymphocytes in vitro as well as in vivo, indicating that cells with high growth requirements can readily upregulate telomerase. Despite detection of telomerase activity, a gr adual telomere erosion occurs in stem cells and lymphocytes, with sign ificantly shortened telomeres at higher ages, a phenomenon that might be of importance for developing immunosenescence and exhausted haemato poiesis. In malignant haematopoietic disorders, telomerase activity is a general finding with large differences in activity levels. The stro ngest telomerase expression has been shown in acute leukaemias and non -Hodgkin's lymphomas, especially high grade cases. There are indicatio ns that the level of activity might parallel tumour progression and be of prognostic relevance, but studies of larger patient materials are needed. An association between the cell cycle and telomerase activity exists, especially for normal haematopoietic cells, and induction of a differentiation programme in immortalised cell lines downregulates te lomerase activity. The expression of telomerase activity seems to be r egulated at different levels, since for immature bone marrow cells the level of activity seemed to parallel better the phenotype than the pr oliferation state. The frequent expression of telomerase in leukaemias and lymphomas makes these disorders interesting targets for future an ti-telomerase therapy. (C) 1997 Elsevier Science Ltd.