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Telomerase activity in normal leukocytes and in hematologic malignancies
CM Counter, J Gupta, CB Harley, B Leber and S Bacchetti
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Telomeres are essential for function and stability of eukaryotic
chromosomes. In the absence of telomerase, the enzyme that synthesizes
telomeric DNA, telomeres shorten with cell division, a process thought to
contribute to cell senescence and the proliferative crisis of transformed
cells. We reported telomere stabilization concomitant with detection of
telomerase activity in cells immortalized in vitro and in ovarian carcinoma
cells, and suggested that telomerase is essential for unlimited cell
proliferation. We have now examined the temporal pattern of telomerase
expression in selected hematologic malignancies. We found that, unlike
other somatic tissues, peripheral, cord blood, and bone marrow leukocytes
from normal donors expressed low levels of telomerase activity. In
leukocytes from chronic lymphocytic leukemia (CLL) patients, activity was
lower than in controls in early disease, and comparable with controls in
late disease. Relative to bone marrow, telomerase activity was enhanced in
myelodysplastic syndrome (MDS) and more significantly so in acute myeloid
leukemia (AML). Regardless of telomerase levels, telomeres shortened with
progression of the diseases. Our results suggest that early CLL and MDS
cells lack an efficient mechanism of telomere maintenance and that
telomerase is activated late in the progression of these cancers,
presumably when critical telomere loss generates selective pressure for
cell immortality.
Volume 85,
Issue 9,
pp. 2315-2320,
05/01/1995
Copyright © 1995 by The American Society of Hematology
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