TELOMERASE ACTIVITY IN NORMAL LEUKOCYTES AND IN HEMATOLOGIC MALIGNANCIES

Telomeres are essential for function and stability of eukaryotic chrom osomes, In the absence of telomerase, the enzyme that synthesizes telo meric DNA, telomeres shorten with cell division, a process thought to contribute to cell senescence and the proliferative crisis of transfor med cells. We reported telomere stabilization concomitant with detecti on of telomerase activity in cells immortalized in vitro and in ovaria n carcinoma cells, and suggested that telomerase is essential for unli mited 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 m arrow leukocytes from normal donors expressed low levels of telomerase activity, In leukocytes from chronic lymphocytic leukemia (CLL) patie nts, activity was lower than in controls in early disease, and compara ble with controls in late disease. Relative to bone marrow, telomerase activity was enhanced in myelodysplastic syndrome (MDS) and more sign ificantly so in acute myeloid leukemia (AML). Regardless of telomerase levels, telomeres shortened with progression of the diseases. Our res ults suggest that early CLL and MDS cells lack an efficient mechanism of telomere maintenance and that telomerase is activated late in the p rogression of these cancers, presumably when critical telomere loss ge nerates selective pressure for cell immortality. (C) 1995 by The Ameri can Society of Hematology.