Telomerase activity in normal leukocytes and in hematologic malignancies.
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.
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C M
CM
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Gupta
J
J
Harley
C B
CB
Leber
B
B
Bacchetti
S
S
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001854:Bone Marrow Cells; D002455:Cell Division; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D004247:DNA / Q000032:analysis; D004253:DNA Nucleotidylexotransferase / Q000032:analysis*; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005312:Fetal Blood / Q000166:cytology; D005347:Fibroblasts; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007962:Leukocytes / Q000201:enzymology*; D008875:Middle Aged; D008954:Models, Biological; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis*; D012867:Skin; D016615:Telomere / Q000737:chemistry*
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D004247:DNA; D004253:DNA Nucleotidylexotransferase