A novel quantitative 'stretch PCR assay', that detects a dramatic increase in telomerase activity during the progression of myeloid leukemias.
Telomerase activation is important for carcinogenesis. However, the timing and magnitude of the activation during cancer development are unknown. In this study, a new PCR-based method for measuring telomerase activity was developed and shown to be very useful for quantitative analysis of human telomerase. Using this assay, blood or bone marrow cells from healthy donors, and patients with chronic myelogenous leukemia (CML) and acute myelogenous leukemia (AML) were examined as to their relative activity. Telomerase activity present in normal peripheral blood cells was generally very low. However, significant activity was detected occasionally in samples derived from younger healthy donors. Striking telomerase activation was observed at the time of the blastic crisis in CML: no samples from chronic phase cases showed significant activity, while all cases with a well established crisis showed strong activity. Most AML cases were telomerase-positive. Quantitative analyses revealed that the relative titer varied among the AML patients, from as low as found in normal cells to as high as found in cell lines. However, a tendency that the activity was higher in relapsed cases than in fresh ones was suggested. In summary, telomerase was activated during the progression of the clinical stages in leukemias. This observation suggests that shortened telomeres and increased telomerase activity might be necessary for cancer cells to undergo clonal evolution towards more malignant phenotypes in advanced stages.
Tatematsu
K
K
Department of Life Science, Tokyo Institute of Technology, Yokohama, Japan.
Nakayama
J
J
Danbara
M
M
Shionoya
S
S
Sato
H
H
Omine
M
M
Ishikawa
F
F
D000328:Adult; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000235:genetics; D004789:Enzyme Activation; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000473:pathology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D004273:DNA, Neoplasm; D019098:Telomerase